Cyclosporine

Summary

Cyclosporine is a steroid-sparing immunosuppressant used in organ and bone marrow transplants as well as inflammatory conditions such as ulcerative colitis, rheumatoid arthritis, and atopic dermatitis.

Brand Names

Cequa, Gengraf, Neoral, Restasis, Sandimmune, Verkazia

Generic Name
Cyclosporine
DrugBank Accession Number
DB00091
Background

Cyclosporine is a calcineurin inhibitor known for its immunomodulatory properties that prevent organ transplant rejection and treat various inflammatory and autoimmune conditions. It is isolated from the fungus Beauveria nivea.2 Initially manufactured by Sandoz and approved for use by the FDA in 1983, cyclosporine is now available in various products by Novartis (previously known as Sandoz).23,24,25

Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Structure

Weight
Average: 1202.635
Monoisotopic: 1201.841368058
Chemical Formula
C62H111N11O12
Synonyms
  • Ciclosporin
  • Ciclosporina
  • Ciclosporine
  • Ciclosporinum
  • CsA
  • CyA
  • Cyclosporin
  • Cyclosporin A
  • Cyclosporine
External IDs
  • 27-400
  • Antibiotic S 7481F1
  • Antibiotic S-7481F1
  • NOVA-22007
  • NSC-290193
  • OL-27-400
  • SANG-35
  • SDZ-OXL-400
Indication

Cyclosporine is approved for a variety of conditions. Firstly, it is approved for the prophylaxis of organ rejection in allogeneic kidney, liver, and heart transplants. It is also used to prevent bone marrow transplant rejection. For the above indications, cyclosporine can be used in conjunction with azathioprine and corticosteroids. Finally, cyclosporine can be used in patients who have chronic transplant rejection and have received previous immunosuppressive therapy20 and to prevent or treat graft-versus-host disease (GVHD).23

Secondly, cyclosporine is used for the treatment of patients with severe active rheumatoid arthritis (RA) when they no longer respond to methotrexate alone.24 It can be used for the treatment of adult non-immunocompromised patients with severe, recalcitrant, plaque psoriasis that have failed to respond to at least one systemic therapy or when systemic therapies are not tolerated or contraindicated.24 The ophthalmic solution of cyclosporine is indicated to increase tear production in patients suffering from keratoconjunctivitis sicca.23 In addition, cyclosporine is approved for the treatment of steroid dependent and steroid-resistant nephrotic syndrome due to glomerular diseases which may include minimal change nephropathy, focal and segmental glomerulosclerosis or membranous glomerulonephritis.23

A cyclosporine ophthalmic emulsion is indicated in the treatment of vernal keratoconjunctivitis in adults and children.27

Off-label, cyclosporine is commonly used for the treatment of various autoimmune and inflammatory conditions such as atopic dermatitis, blistering disorders, ulcerative colitis, juvenile rheumatoid arthritis, uveitis, connective tissue diseases, as well as idiopathic thrombocytopenic purpura.1,17,6,7,8

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Associated Conditions
  • Atopic Dermatitis
  • Bone Marrow Transplant Rejection
  • Chronic transplant rejection
  • Connective Tissue Disorders
  • Focal Segmental Glomerulosclerosis (FSGS)
  • Graft Versus Host Disease (cGvHD)
  • Heart Transplant Rejection
  • Immune Thrombocytopenia (ITP)
  • Interstitial Cystitis
  • Juvenile Idiopathic Arthritis (JIA)
  • Kidney Transplant Rejection
  • Liver Transplant Rejection
  • Lupus Nephritis
  • Nephrotic Syndrome
  • Ocular Rosacea
  • Severe Ulcerative Colitis
  • Steroid Dependent Nephrotic Syndrome
  • Steroid Resistant Nephrotic Syndrome
  • Transplanted Organ Rejection
  • Uveitis
  • Vernal Keratoconjunctivitis
  • Blistering disorder
  • Refractory Ulcerative colitis
  • Severe, active Rheumatoid arthritis
  • Severe, recalcitrant Plaque psoriasis
  • Suppressed tear production
Contraindications & Blackbox Warnings

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Pharmacodynamics

Cyclosporine exerts potent immunosuppressive actions on T cells, thereby prolonging survival following organ and bone marrow transplants.24 This drug prevents and controls serious immune-mediated reactions including allograft rejection, graft versus host disease, and inflammatory autoimmune disease.24

Some notable effects of cyclosporine are hypertrichosis, gingival hyperplasia, and hyperlipidemia. There is also some debate about this drug causing nephrotoxicity.9

Mechanism of action

Cyclosporine is a calcineurin inhibitor that inhibits T cell activation.2,5,12 Its binding to the receptor cyclophilin-1 inside cells produces a complex known as cyclosporine-cyclophilin. This complex subsequently inhibits calcineurin, which in turn stops the dephosphorylation as well as the activation of the nuclear factor of activated T cells (NF-AT) that normally cause inflammatory reactions. NF-AT is a transcription factor that promotes the production of cytokines such as IL-2, IL-4, interferon-gamma and TNF-alpha, all of which are involved in the inflammatory process. Specifically, the inhibition of IL-2, which is necessary for T cell activation or proliferation, is believed to be responsible for cyclosporine's immunosuppressive actions.2,11 In addition to the above, the inhibition of NF-AT leads to lower levels of other factors associated with T helper cell function and thymocyte development.2

Target Actions Organism
ACalcium signal-modulating cyclophilin ligand

binder

 Humans
ACalcineurin subunit B type 2

inhibitor

 Humans
APeptidyl-prolyl cis-trans isomerase A

inhibitor

binder

 Humans
APeptidyl-prolyl cis-trans isomerase F, mitochondrial

binder

 Humans
Absorption

The absorption of cyclosporine occurs mainly in the intestine.2,10 Absorption of cyclosporine is highly variable with a peak bioavailability of 30% sometimes occurring 1-8 hours after administration with a second peak observed in certain patients.5,23 The absorption of cyclosporine from the GI tract has been found to be incomplete, likely due to first pass effects.9 Cmax in both the blood and plasma occurs at approximately 3.5 hours post-dose.20

The Cmax of a 0.1% cyclosporine ophthalmic emulsion is 0.67 ng/mL after instilling one drop four times daily.27

A note on erratic absorption

During chronic administration, the absorption of Sandimmune Soft Gelatin Capsules and Oral Solution have been observed to be erratic, according to Novartis prescribing information. Those being administered the soft gelatin capsules or oral solution over the long term should be regularly monitored by testing cyclosporine blood concentrations and adjusting the dose accordingly.20 When compared with the other oral forms of Sandimmune, Neoral capsules and solution have a higher rate of absorption that results in a higher Tmax and a 59% higher Cmax with a 29 % higher bioavailability.20

Volume of distribution

The distribution of cyclosporine in the blood consists of 33%-47% in plasma, 4%-9% in the lymphocytes, 5%-12% in the granulocytes, and 41%-58% in the erythrocytes.20 The reported volume of distribution of cyclosporine ranges from 4-8 L/kg. It concentrates mainly in leucocyte-rich tissues as well as tissues that contain high amounts of fat because it is highly lipophilic.9 Cyclosporine, in the eye drop formulation, crosses the blood-retinal barrier.5,13

Protein binding

About 50% of the administered dose is taken up by erythrocytes while about 34% is bound to lipoproteins.5 Prescribing information for Sandimmune states that 90% is mainly bound to lipoproteins.20

Metabolism

Cyclosporine is metabolized in the intestine and the liver by CYP450 enzymes, predominantly CYP3A4 with contributions from CYP3A5.2,9 The involvement of CYP3A7 is not clearly established.9 Cyclosporine undergoes several metabolic pathways and about 25 different metabolites have been identified. One of its main active metabolites, AM1, demonstrates only 10-20% activity when compared to the parent drug, according to some studies.5,9

The 3 primary metabolites are M1, M9, and M4N, which are produced from oxidation at the 1-beta, 9-gamma, and 4-N-demethylated positions, respectively.9

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Route of elimination

After sulfate conjugation, cyclosporine remains in the bile where it is broken down to the original compound and then re-absorbed into the circulation. Cyclosporine excretion is primarily biliary with only 3-6%9,20 of the dose (including the parent drug and metabolites) excreted in the urine while 90% of the administered dose is eliminated in the bile. From the excreted proportion, under 1% of the dose is excreted as unchanged cyclosporine.5,20

Half-life

The half-life of cyclosporine is biphasic and very variable on different conditions but it is reported in general to last 19 hours.5 Prescribing information also states a terminal half-life of approximately 19 hours, but with a range between 10 to 27 hours.20

Clearance

Cyclosporin shows a linear clearance profile that ranges from 0.38 to 3 Lxh/kg5, however, there is substantial inter- patient variability.9 A 250 mg dose of cyclosporine in the oral soft gelatin capsule of a lipid micro-emulsion formulation shows an approximate clearance of 22.5 L/h.14

Adverse Effects

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Toxicity

The oral LD50 in rats is 1480 mg/kg and the TDLO in humans is 12 mg/kg.21

Overdose information

In cases of overdose with oral cyclosporine, forced emesis and gastric lavage are recommended 2 hours after ingestion. There are little data available in the literature regarding overdoses with cyclosporine, but hepatotoxicity and nephrotoxicity may occur.24 One case report of an cyclosporine overdose due to medical error was made involving a 26 year old female and noted the occurrence of nausea, flushing, tremor, vertigo and vomiting, which resolved within about 1 day. Anorexia and a feeling of increased body girth were also experienced by this patient and resolved within about 2 weeks.14 When overdose with cyclosporine is observed, it is important to consider that dialysis and charcoal, hemoperfusion are not effective techniques to remove cyclosporine from the body.24

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available
Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

  • Approved
  • Vet approved
  • Nutraceutical
  • Illicit
  • Withdrawn
  • Investigational
  • Experimental
  • All Drugs
Drug Interaction

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interactions in your software
1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Cyclosporine.
Abacavir Cyclosporine may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abametapir The serum concentration of Cyclosporine can be increased when it is combined with Abametapir.
Abatacept Abatacept may increase the immunosuppressive activities of Cyclosporine.
Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Cyclosporine.
Abiraterone The metabolism of Abiraterone can be decreased when combined with Cyclosporine.
Abrocitinib The serum concentration of Cyclosporine can be increased when it is combined with Abrocitinib.
Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Cyclosporine.
Acebutolol The metabolism of Acebutolol can be decreased when combined with Cyclosporine.
Aceclofenac The risk or severity of renal failure and hypertension can be increased when Aceclofenac is combined with Cyclosporine.
Food Interactions
  • Avoid grapefruit products.
  • Avoid potassium-containing products. Taking products that increase serum potassium may increase the risk of hyperkalemia.
  • Avoid St. John's Wort.
  • Take at the same time every day. Take consistently with regard to food.

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Product Images
International/Other Brands
Sangcya (Sangstat Medical Corp.) / Verkazia (Santen Inc.)
Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
Aqua-stasis Liquid 0.0005 g/100mL Ophthalmic Dr Marc's Manufacturing And Sales 2016-02-23 2018-04-17 US flag
Cequa Solution 0.09 % w/v Ophthalmic Sun Pharmaceutical Industries Ltd. 2021-11-04 Not applicable Canada flag
Cequa Solution / drops 0.0009 mg/1mL Ophthalmic; Topical Sun Pharmaceutical Industries, Inc. 2018-08-15 Not applicable US flag
Cequa Solution / drops 0.0009 g/1mL Ophthalmic; Topical Sun Pharmaceutical Industries, Inc. 2018-08-15 Not applicable US flag
Cyclo-derm Liquid 0.25 g/100mL Topical Dr Marc's Manufacturing And Sales 2016-02-23 2018-04-17 US flag
Cyclosporine Capsule 25 mg Oral Sandoz Canada Incorporated Not applicable Not applicable Canada flag
Cyclosporine Injection, solution 50 mg/1mL Intravenous AMERICAN REGENT, INC. 2003-10-07 2021-04-30 US flag
Cyclosporine Capsules Capsule 25 mg Oral Strides Pharma Canada Inc 2022-02-03 Not applicable Canada flag
Cyclosporine Capsules Capsule 50 mg Oral Strides Pharma Canada Inc 2022-02-03 Not applicable Canada flag
Cyclosporine Capsules Capsule 100 mg Oral Strides Pharma Canada Inc 2022-02-03 Not applicable Canada flag
Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
Apo-cyclosporine Oral Solution Solution 100 mg / mL Oral Apotex Corporation 2002-07-30 Not applicable Canada flag
Cyclosporine Capsule, liquid filled 100 mg/1 Oral Strides Pharma Science Limited 2022-08-16 Not applicable US flag
Cyclosporine Capsule, liquid filled 100 mg/1 Oral Physicians Total Care, Inc. 2006-02-10 Not applicable US flag
Cyclosporine Emulsion 0.5 mg/1mL Ophthalmic A-S Medication Solutions 2022-02-07 Not applicable US flag
Cyclosporine Capsule 25 mg/1 Oral Eon Labs, Inc. 2000-01-13 2020-03-31 US flag
Cyclosporine Solution 100 mg/1mL Oral Teva Pharmaceuticals USA, Inc. 2005-03-29 Not applicable US flag
CycloSPORINE Solution 100 mg/1mL Oral Actavis Pharma, Inc. 2008-12-01 2016-07-31 US flag
Cyclosporine Emulsion 0.5 mg/1mL Ophthalmic KVK-Tech, Inc. 2022-02-10 Not applicable US flag
Cyclosporine Capsule, gelatin coated 100 mg/1 Oral American Health Packaging 2015-11-03 Not applicable US flag
Cyclosporine Injection, solution 50 mg/1mL Intravenous Bedford Pharmaceuticals 1999-12-15 2012-02-29 US flag
Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image
Aqua-stasis Cyclosporine (0.0005 g/100mL) Liquid Ophthalmic Dr Marc's Manufacturing And Sales 2016-02-23 2018-04-17 US flag
Cyclo-derm Cyclosporine (0.25 g/100mL) Liquid Topical Dr Marc's Manufacturing And Sales 2016-02-23 2018-04-17 US flag
Cyclosporine Cyclosporine (50 mg/1mL) Injection, solution Intravenous AMERICAN REGENT, INC. 2003-10-07 2021-04-30 US flag
Cyclosporine/Chondroitin PF Cyclosporine (1 mg/1mL) Emulsion Ophthalmic Imprimis Njof, Llc 2018-07-01 Not applicable US flag
Cyclosporine/Chondroitin Sulfate PF Cyclosporine (1 mg/1mL) Emulsion Ophthalmic ImprimisRx NJ 2018-02-01 Not applicable US flag
Hydro-stasis Cyclosporine (0.0005 g/100mL) Liquid Ophthalmic Dr Marc's Manufacturing And Sales 2016-02-23 2018-04-17 US flag
Nail Cyclosporin-A Cyclosporine (0.25 g/100mL) Liquid Topical Dr Marc's Manufacturing And Sales 2016-02-23 2018-04-17 US flag
ATC Codes
L04AD01 — Ciclosporin
  • L04AD — Calcineurin inhibitors
  • L04A — IMMUNOSUPPRESSANTS
  • L04 — IMMUNOSUPPRESSANTS
  • L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
S01XA18 — Ciclosporin
  • S01XA — Other ophthalmologicals
  • S01X — OTHER OPHTHALMOLOGICALS
  • S01 — OPHTHALMOLOGICALS
  • S — SENSORY ORGANS
Drug Categories
  • Agents causing hyperkalemia
  • Agents Causing Muscle Toxicity
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  • Agents that reduce seizure threshold
  • Amino Acids, Peptides, and Proteins
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  • Calcineurin Inhibitor Immunosuppressant
  • Calcineurin Inhibitors
  • Cyclosporins
  • Cytochrome P-450 CYP2C19 Inhibitors
  • Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 CYP2D6 Inhibitors (moderate)
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  • Peptides
  • Peptides, Cyclic
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as cyclosporins. These are cyclic depsipeptides containing the cyclosporin backbone.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Peptoid-peptide hybrids
Direct Parent
Cyclosporins
Alternative Parents
Oligopeptides / Macrolactams / Alpha amino acids and derivatives / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Secondary alcohols / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds show 3 more
Substituents
Alcohol / Aliphatic heteromonocyclic compound / Alpha-amino acid or derivatives / Alpha-oligopeptide / Azacycle / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Cyclosporin-backbone / Hydrocarbon derivative / Lactam / Macrolactam / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Secondary alcohol / Secondary carboxylic acid amide / Tertiary carboxylic acid amide show 12 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
homodetic cyclic peptide (CHEBI:4031)
Affected organisms
  • Humans and other mammals
UNII
83HN0GTJ6D
CAS number
59865-13-3
InChI Key
PMATZTZNYRCHOR-CGLBZJNRSA-N
InChI

InChI=1S/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+/t40-,41+,42-,43+,44+,45+,46+,47+,49+,50+,51+,52-/m1/s1

IUPAC Name

(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(1R,2R,4E)-1-hydroxy-2-methylhex-4-en-1-yl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-bis(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecaazacyclotritriacontan-2,5,8,11,14,17,20,23,26,29,32-undecone

SMILES

CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C

Synthesis Reference

Hans Dietl, "Pharmaceutical preparation containing cyclosporine(s) for intravenous administration and a process for its production." U.S. Patent US5527537, issued October, 1990.

US5527537
General References
  1. Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S: Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994 Jun 30;330(26):1841-5. [Article]
  2. Forsythe P, Paterson S: Ciclosporin 10 years on: indications and efficacy. Vet Rec. 2014 Mar;174 Suppl 2:13-21. doi: 10.1136/vr.102484. [Article]
  3. Cockerill GW, Bert AG, Ryan GR, Gamble JR, Vadas MA, Cockerill PN: Regulation of granulocyte-macrophage colony-stimulating factor and E-selectin expression in endothelial cells by cyclosporin A and the T-cell transcription factor NFAT. Blood. 1995 Oct 1;86(7):2689-98. [Article]
  4. Lallemand F, Schmitt M, Bourges JL, Gurny R, Benita S, Garrigue JS: Cyclosporine A delivery to the eye: A comprehensive review of academic and industrial efforts. Eur J Pharm Biopharm. 2017 Aug;117:14-28. doi: 10.1016/j.ejpb.2017.03.006. Epub 2017 Mar 14. [Article]
  5. Faulds D, Goa KL, Benfield P: Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs. 1993 Jun;45(6):953-1040. doi: 10.2165/00003495-199345060-00007. [Article]
  6. Kappers-Klunne MC, van't Veer MB: Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy. Br J Haematol. 2001 Jul;114(1):121-5. doi: 10.1046/j.1365-2141.2001.02893.x. [Article]
  7. Lee SH, Chung H, Yu HG: Clinical outcomes of cyclosporine treatment for noninfectious uveitis. Korean J Ophthalmol. 2012 Feb;26(1):21-5. doi: 10.3341/kjo.2012.26.1.21. Epub 2012 Jan 14. [Article]
  8. Yang TH, Wu TH, Chang YL, Liao HT, Hsu CC, Tsai CY, Chou YC: Cyclosporine for the treatment of lupus nephritis in patients with systemic lupus erythematosus. Clin Nephrol. 2018 Apr;89(4):277-285. doi: 10.5414/CN109325. [Article]
  9. Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB: PharmGKB summary: cyclosporine and tacrolimus pathways. Pharmacogenet Genomics. 2013 Oct;23(10):563-85. doi: 10.1097/FPC.0b013e328364db84. [Article]
  10. Freeman DJ: Pharmacology and pharmacokinetics of cyclosporine. Clin Biochem. 1991 Feb;24(1):9-14. doi: 10.1016/0009-9120(91)90084-r. [Article]
  11. Russell G, Graveley R, Seid J, al-Humidan AK, Skjodt H: Mechanisms of action of cyclosporine and effects on connective tissues. Semin Arthritis Rheum. 1992 Jun;21(6 Suppl 3):16-22. doi: 10.1016/0049-0172(92)90009-3. [Article]
  12. Kapturczak MH, Meier-Kriesche HU, Kaplan B: Pharmacology of calcineurin antagonists. Transplant Proc. 2004 Mar;36(2 Suppl):25S-32S. doi: 10.1016/j.transproceed.2004.01.018. [Article]
  13. Occhiutto ML, Freitas FR, Maranhao RC, Costa VP: Breakdown of the blood-ocular barrier as a strategy for the systemic use of nanosystems. Pharmaceutics. 2012 May 14;4(2):252-75. doi: 10.3390/pharmaceutics4020252. [Article]
  14. Tafazoli A: Accidental Overdose of Oral Cyclosporine in Haematopoietic Stem Cell Transplantation: A Case Report and Literature Review. Drug Saf Case Rep. 2015 Dec;2(1):20. doi: 10.1007/s40800-015-0023-3. [Article]
  15. Flechner SM, Katz AR, Rogers AJ, Van Buren C, Kahan BD: The presence of cyclosporine in body tissues and fluids during pregnancy. Am J Kidney Dis. 1985 Jan;5(1):60-3. doi: 10.1016/s0272-6386(85)80138-4. [Article]
  16. Nyberg G, Haljamae U, Frisenette-Fich C, Wennergren M, Kjellmer I: Breast-feeding during treatment with cyclosporine. Transplantation. 1998 Jan 27;65(2):253-5. doi: 10.1097/00007890-199801270-00019. [Article]
  17. Dehesa L, Abuchar A, Nuno-Gonzalez A, Vitiello M, Kerdel FA: The use of cyclosporine in dermatology. J Drugs Dermatol. 2012 Aug;11(8):979-87. [Article]
  18. FDA approvals [Link]
  19. Dailymed [Link]
  20. Cyclosporine Product Label [Link]
  21. Cayman Chem: Cyclosporine MSDS [Link]
  22. NIH Stat Pearls: Cyclosporine [Link]
  23. Novartis Monograph: Apo-Cyclosporine [Link]
  24. Neoral (Cyclosporine) FDA Label [Link]
  25. NY times: Drug that reduces risk in transplants gets early approval [Link]
  26. FDA Approved Products: Restasis (cyclosporine ophthalmic emulsion) [Link]
  27. FDA Approved Drug Products: Verkazia (Cyclosporine) Ophthalmic Emulsion [Link]
  28. NEORAL (cyclosporine) HC label [File]
KEGG Drug
D00184
KEGG Compound
C05086
PubChem Compound
5284373
PubChem Substance
46508198
ChemSpider
4447449
BindingDB
50022815
RxNav
3008
ChEBI
4031
ChEMBL
CHEMBL160
Therapeutic Targets Database
DNC001177
PharmGKB
PA449167
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ciclosporin
FDA label
MSDS
Clinical Trials
Phase Status Purpose Conditions Count
4 Active Not Recruiting Health Services Research Liver Transplantation 1
4 Active Not Recruiting Treatment Dry Eye Syndrome (DES) 1
4 Completed Not Available Cataracts / Dry Eyes 1
4 Completed Not Available Dry Eyes 1
4 Completed Not Available Endothelial Graft Rejection 1
4 Completed Not Available Pterygium 1
4 Completed Basic Science End Stage Renal Disease (ESRD) 1
4 Completed Diagnostic Acute Renal Failure (ARF) / Heart Transplantation 1
4 Completed Diagnostic Cardiac Transplant 1
4 Completed Diagnostic Heart and Lung Transplant 1
Manufacturers
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  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Pliva inc
  • Sandoz inc
  • Abbott laboratories
  • Novartis pharmaceuticals corp
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  • Bedford laboratories div ben venue laboratories inc
  • Pharmaforce inc
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  • Watson laboratories inc
  • Wockhardt eu operations (swiss) ag
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  • Abbott Laboratories Ltd.
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  • Cardinal Health
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  • Eon Labs
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  • Lake Erie Medical and Surgical Supply
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Novartis AG
  • Paddock Labs
  • Physicians Total Care Inc.
  • Pliva Inc.
  • R.P. Scherer GmbH and Co. KG
  • Sandhills Packaging Inc.
  • Sangstat Medical Corp.
  • Santec Chemicals Corp.
  • Swiss Caps Ag
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Watson Pharmaceuticals
  • Wockhardt Ltd.
Dosage Forms
Form Route Strength
Capsule, liquid filled Oral 50 mg
Capsule, liquid filled Oral 25 mg
Solution Ophthalmic 0.09 % w/v
Solution / drops Ophthalmic; Topical 0.0009 mg/1mL
Solution / drops Ophthalmic; Topical 0.0009 g/1mL
Solution Oral 100 mg
Capsule, liquid filled Oral 100 mg
Liquid Topical 0.25 g/100mL
Capsule Oral 100 mg/1
Capsule, gelatin coated Oral 100 mg/1
Capsule, gelatin coated Oral 25 mg/1
Capsule, liquid filled Oral 100 mg/1
Injection, solution Intravenous 50 mg/1mL
Solution Oral 100 mg/1mL
Powder Not applicable 1 g/1g
Capsule, liquid filled Oral 25 mg/1
Capsule, liquid filled Oral 50 mg/1
Emulsion Ophthalmic 1 mg/1mL
Capsule, liquid filled Oral 100.00 MG
Capsule, liquid filled Oral 25.00 MG
Capsule, liquid filled Oral 50.00 MG
Capsule, gelatin coated Oral
Capsule Oral 50 mg
Capsule Oral 25 mg/1
Capsule Oral 50 mg/1
Liquid Ophthalmic 0.0005 g/100mL
Liquid Ophthalmic 1 mg/1ml
Solution / drops Ophthalmic 1 MG/ML
Solution / drops Ophthalmic
Emulsion Ophthalmic 1 mg/ml
Capsule, liquid filled Oral 10 mg
Tablet Oral 25 mg
Solution Oral 10 g
Solution Conjunctival; Ophthalmic 1 mg
Solution Oral
Capsule Oral
Capsule Oral 10 mg
Solution Oral 100 mg / mL
Capsule, gelatin coated Oral 100 mg
Capsule, gelatin coated Oral 25 mg
Capsule, gelatin coated Oral 50 mg
Emulsion Ophthalmic 0.05 % w/v
Emulsion Ophthalmic 0.5 mg/1mL
Emulsion Ophthalmic
Emulsion Conjunctival 0.2 mg
Injection, solution, concentrate Intravenous; Parenteral 50 MG/ML
Injection, solution Intravenous
Solution 50 mg/1ml
Injection, solution, concentrate Parenteral 50 mg/ml
Injection Intravenous 50.0 mg/ml
Injection Intravenous
Solution Oral 100 MG/ML
Capsule Oral 100 mg
Capsule Oral 25 mg
Capsule, liquid filled Oral 10.0 mg
Capsule, liquid filled Oral 100.0 mg
Capsule, liquid filled Oral 25.0 mg
Capsule, liquid filled Oral 50.0 mg
Solution Oral 100.0 mg/ml
Emulsion Oral 10 g
Solution Intravenous 0.05 g
Injection Intravenous 50 mg/1mL
Solution Intravenous 50 mg / mL
Liquid Oral 100 mg / mL
Emulsion Ophthalmic 0.1 % w/v
Emulsion Ophthalmic; Topical 1 mg/1mL
Prices
Unit description Cost Unit
SandIMMUNE 100 mg/ml Solution 50ml Bottle 499.62USD bottle
Neoral 100 mg/ml Solution 50ml Bottle 346.14USD bottle
CycloSPORINE Modified 100 mg/ml Solution 50ml Bottle 311.53USD bottle
SandIMMUNE 30 100 mg capsule Box 308.69USD box
Restasis 30 0.05% Emulsion 1 Box = 30 Containers 205.99USD box
Neoral 30 100 mg capsule Box 190.54USD box
CycloSPORINE Modified 30 100 mg capsule Box 171.48USD box
Gengraf 30 100 mg capsule Box 159.94USD box
SandIMMUNE 30 25 mg capsule Box 77.33USD box
Neoral 30 25 mg capsule Box 47.69USD box
SandIMMUNE 50 mg/ml Solution 5ml Ampule 46.38USD ampule
Gengraf 30 25 mg capsule Box 42.99USD box
CycloSPORINE Modified 30 25 mg capsule Box 42.9USD box
Cyclosporine a powder 25.2USD g
Sandimmune 100 mg capsule 9.89USD capsule
Sandimmune 50 mg/ml ampul 7.71USD ml
Cyclosporine 100 mg capsule 6.46USD capsule
Neoral 100 mg gelatn capsule 6.11USD capsule
Cyclosporine 100 mg softgel 5.5USD softgel capsule
Cyclosporine modif 100 mg softgel 5.5USD softgel capsule
Cyclosporine modif 100 mg capsule 5.49USD capsule
Cyclosporine 50 mg/ml amp 5.45USD ml
Cyclosporine 50 mg/ml vial 5.28USD ml
Gengraf 100 mg capsule 5.28USD capsule
Restasis 0.05% eye emulsion 4.49USD each
Cyclosporine 50 mg softgel 2.74USD softgel capsule
Sandimmune 25 mg capsule 2.48USD capsule
Cyclosporine 25 mg capsule 1.56USD capsule
Neoral 25 mg gelatin capsule 1.53USD capsule
Cyclosporine 25 mg softgel 1.38USD softgel capsule
Gengraf 25 mg capsule 1.32USD capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region
US5985321 No 1999-11-16 2014-09-26 US flag
US4839342 No 1989-06-13 2009-08-02 US flag
CA2108018 No 2003-04-15 2012-04-16 Canada flag
CA1332150 No 1994-09-27 2011-09-27 Canada flag
US8633162 No 2014-01-21 2024-08-27 US flag
US8648048 No 2014-02-11 2024-08-27 US flag
US9248191 No 2016-02-02 2024-08-27 US flag
US8629111 No 2014-01-14 2024-08-27 US flag
US8642556 No 2014-02-04 2024-08-27 US flag
US8685930 No 2014-04-01 2024-08-27 US flag
US8561859 No 2013-10-22 2032-04-16 US flag
US9676525 No 2017-06-13 2034-02-07 US flag
US8292129 No 2012-10-23 2031-02-25 US flag
US9669974 No 2017-06-06 2034-05-11 US flag
US9937225 No 2018-04-10 2033-08-23 US flag
US8980839 No 2015-03-17 2033-08-23 US flag
US10441630 No 2019-10-15 2033-08-23 US flag
US10918694 No 2021-02-16 2037-02-28 US flag
US8298568 No 2012-10-30 2027-11-03 US flag
US9220694 No 2015-12-29 2026-01-27 US flag
US7973081 No 2011-07-05 2026-01-27 US flag
US8524779 No 2013-09-03 2026-01-27 US flag
US9132071 No 2015-09-15 2029-06-02 US flag
US9956289 No 2018-05-01 2026-01-27 US flag
State
Solid
Experimental Properties
Property Value Source
melting point (°C) 148-151 °C https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5163816.htm
boiling point (°C) 838.63 https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5163816.htm
water solubility insoluble https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5163816.htm
logP 1.4 https://www.sciencedirect.com/science/article/pii/S0939641116309080
Caco2 permeability -6.05 ADME Research, USCD
pKa 13.32±0.70 https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5163816.htm
Predicted Properties
Property Value Source
logP 3.64 ChemAxon
pKa (Strongest Acidic) 11.83 ChemAxon
pKa (Strongest Basic) -2.4 ChemAxon
Physiological Charge 0 ChemAxon
Hydrogen Acceptor Count 12 ChemAxon
Hydrogen Donor Count 5 ChemAxon
Polar Surface Area 278.8 Å2 ChemAxon
Rotatable Bond Count 15 ChemAxon
Refractivity 327.14 m3·mol-1 ChemAxon
Polarizability 133.6 Å3 ChemAxon
Number of Rings 1 ChemAxon
Bioavailability 0 ChemAxon
Rule of Five No ChemAxon
Ghose Filter No ChemAxon
Veber's Rule No ChemAxon
MDDR-like Rule No ChemAxon
Predicted ADMET Features
Property Value Probability
Human Intestinal Absorption + 0.8727
Blood Brain Barrier - 0.9659
Caco-2 permeable - 0.6994
P-glycoprotein substrate Substrate 0.8463
P-glycoprotein inhibitor I Inhibitor 0.8685
P-glycoprotein inhibitor II Non-inhibitor 0.5992
Renal organic cation transporter Non-inhibitor 0.9485
CYP450 2C9 substrate Non-substrate 0.8628
CYP450 2D6 substrate Non-substrate 0.8823
CYP450 3A4 substrate Substrate 0.6407
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 inhibitor Non-inhibitor 0.923
CYP450 2D6 inhibitor Non-inhibitor 0.9265
CYP450 2C19 inhibitor Non-inhibitor 0.9026
CYP450 3A4 inhibitor Non-inhibitor 0.6112
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9968
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.8948
Biodegradation Not ready biodegradable 0.9244
Rat acute toxicity 2.8788 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9815
hERG inhibition (predictor II) Non-inhibitor 0.9214

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action

Yes

Actions

Binder

General Function
Not Available
Specific Function
Likely involved in the mobilization of calcium as a result of the TCR/CD3 complex interaction. Binds to cyclophilin B.
Gene Name
CAMLG
Uniprot ID
P49069
Uniprot Name
Calcium signal-modulating cyclophilin ligand
Molecular Weight
32952.255 Da
References
  1. Bernasconi R, Solda T, Galli C, Pertel T, Luban J, Molinari M: Cyclosporine A-sensitive, cyclophilin B-dependent endoplasmic reticulum-associated degradation. PLoS One. 2010 Sep 28;5(9). pii: e13008. doi: 10.1371/journal.pone.0013008. [Article]
  2. Yamashita H, Ito T, Kato H, Asai S, Tanaka H, Nagai H, Inagaki N: Comparison of the efficacy of tacrolimus and cyclosporine A in a murine model of dinitrofluorobenzene-induced atopic dermatitis. Eur J Pharmacol. 2010 Oct 25;645(1-3):171-6. doi: 10.1016/j.ejphar.2010.07.031. Epub 2010 Aug 3. [Article]
  3. Galat A, Bua J: Molecular aspects of cyclophilins mediating therapeutic actions of their ligands. Cell Mol Life Sci. 2010 Oct;67(20):3467-88. doi: 10.1007/s00018-010-0437-0. Epub 2010 Jul 4. [Article]
  4. Lee J, Kim SS: Current implications of cyclophilins in human cancers. J Exp Clin Cancer Res. 2010 Jul 19;29:97. doi: 10.1186/1756-9966-29-97. [Article]
  5. Forsythe P, Paterson S: Ciclosporin 10 years on: indications and efficacy. Vet Rec. 2014 Mar;174 Suppl 2:13-21. doi: 10.1136/vr.102484. [Article]
  6. Russell G, Graveley R, Seid J, al-Humidan AK, Skjodt H: Mechanisms of action of cyclosporine and effects on connective tissues. Semin Arthritis Rheum. 1992 Jun;21(6 Suppl 3):16-22. doi: 10.1016/0049-0172(92)90009-3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Yes

Actions

Inhibitor

General Function
Calcium ion binding
Specific Function
Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity (By similarity).
Gene Name
PPP3R2
Uniprot ID
Q96LZ3
Uniprot Name
Calcineurin subunit B type 2
Molecular Weight
19533.065 Da
References
  1. Yamashita H, Ito T, Kato H, Asai S, Tanaka H, Nagai H, Inagaki N: Comparison of the efficacy of tacrolimus and cyclosporine A in a murine model of dinitrofluorobenzene-induced atopic dermatitis. Eur J Pharmacol. 2010 Oct 25;645(1-3):171-6. doi: 10.1016/j.ejphar.2010.07.031. Epub 2010 Aug 3. [Article]
  2. Grigoriu S, Bond R, Cossio P, Chen JA, Ly N, Hummer G, Page R, Cyert MS, Peti W: The molecular mechanism of substrate engagement and immunosuppressant inhibition of calcineurin. PLoS Biol. 2013;11(2):e1001492. doi: 10.1371/journal.pbio.1001492. Epub 2013 Feb 26. [Article]
  3. Cardenas ME, Hemenway C, Muir RS, Ye R, Fiorentino D, Heitman J: Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands. EMBO J. 1994 Dec 15;13(24):5944-57. [Article]
  4. Neoral (Cyclosporine) FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action

Yes

Actions

Inhibitor

Binder

Cyclosporin A has been shown to inhibit cyclophilin.
General Function
Virion binding
Specific Function
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Gene Name
PPIA
Uniprot ID
P62937
Uniprot Name
Peptidyl-prolyl cis-trans isomerase A
Molecular Weight
18012.42 Da
References
  1. Redell JB, Zhao J, Dash PK: Acutely increased cyclophilin a expression after brain injury: a role in blood-brain barrier function and tissue preservation. J Neurosci Res. 2007 Jul;85(9):1980-8. [Article]
  2. Schaller T, Ylinen LM, Webb BL, Singh S, Towers GJ: Fusion of cyclophilin A to Fv1 enables cyclosporine-sensitive restriction of human and feline immunodeficiency viruses. J Virol. 2007 Sep;81(18):10055-63. Epub 2007 Jul 3. [Article]
  3. Lee J, Kim SS: Current implications of cyclophilins in human cancers. J Exp Clin Cancer Res. 2010 Jul 19;29:97. doi: 10.1186/1756-9966-29-97. [Article]
  4. Stegmann CM, Luhrmann R, Wahl MC: The crystal structure of PPIL1 bound to cyclosporine A suggests a binding mode for a linear epitope of the SKIP protein. PLoS One. 2010 Apr 2;5(4):e10013. doi: 10.1371/journal.pone.0010013. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Yes

Actions

Binder

General Function
Peptidyl-prolyl cis-trans isomerase activity
Specific Function
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Involved in regulation of the mitochondrial permeability trans...
Gene Name
PPIF
Uniprot ID
P30405
Uniprot Name
Peptidyl-prolyl cis-trans isomerase F, mitochondrial
Molecular Weight
22040.09 Da
References
  1. Quesniaux VF, Schreier MH, Wenger RM, Hiestand PC, Harding MW, Van Regenmortel MH: Molecular characteristics of cyclophilin-cyclosporine interaction. Transplantation. 1988 Aug;46(2 Suppl):23S-28S. doi: 10.1097/00007890-198808001-00005. [Article]
  2. Ryffel B, Woerly G, Greiner B, Haendler B, Mihatsch MJ, Foxwell BM: Distribution of the cyclosporine binding protein cyclophilin in human tissues. Immunology. 1991 Mar;72(3):399-404. [Article]
  3. Kallen J, Spitzfaden C, Zurini MG, Wider G, Widmer H, Wuthrich K, Walkinshaw MD: Structure of human cyclophilin and its binding site for cyclosporin A determined by X-ray crystallography and NMR spectroscopy. Nature. 1991 Sep 19;353(6341):276-9. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Inhibitor

Data regarding this enzyme action of cyclosporin is limited to the results of one in vitro study. Clinical correlation is unknown.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Niwa T, Yamamoto S, Saito M, Shiraga T, Takagi A: Effect of cyclosporine and tacrolimus on cytochrome p450 activities in human liver microsomes. Yakugaku Zasshi. 2007 Jan;127(1):209-16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Inhibitor

Data regarding this enzyme action of cyclosporin is limited to the results of one in vitro study. Clinical correlation is unknown.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Niwa T, Yamamoto S, Saito M, Shiraga T, Takagi A: Effect of cyclosporine and tacrolimus on cytochrome p450 activities in human liver microsomes. Yakugaku Zasshi. 2007 Jan;127(1):209-16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Substrate

General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Zhu HJ, Yuan SH, Fang Y, Sun XZ, Kong H, Ge WH: The effect of CYP3A5 polymorphism on dose-adjusted cyclosporine concentration in renal transplant recipients: a meta-analysis. Pharmacogenomics J. 2011 Jun;11(3):237-46. doi: 10.1038/tpj.2010.26. Epub 2010 Apr 6. [Article]
  2. Zheng S, Tasnif Y, Hebert MF, Davis CL, Shitara Y, Calamia JC, Lin YS, Shen DD, Thummel KE: CYP3A5 gene variation influences cyclosporine A metabolite formation and renal cyclosporine disposition. Transplantation. 2013 Mar 27;95(6):821-7. doi: 10.1097/TP.0b013e31827e6ad9. [Article]
  3. Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB: PharmGKB summary: cyclosporine and tacrolimus pathways. Pharmacogenet Genomics. 2013 Oct;23(10):563-85. doi: 10.1097/FPC.0b013e328364db84. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. Neoral (Cyclosporine) FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Substrate

Inhibitor

General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [Article]
  2. Sidharta PN, Treiber A, Dingemanse J: Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan. Clin Pharmacokinet. 2015 May;54(5):457-71. doi: 10.1007/s40262-015-0255-5. [Article]
  3. Amundsen R, Asberg A, Ohm IK, Christensen H: Cyclosporine A- and tacrolimus-mediated inhibition of CYP3A4 and CYP3A5 in vitro. Drug Metab Dispos. 2012 Apr;40(4):655-61. doi: 10.1124/dmd.111.043018. Epub 2011 Dec 28. [Article]
  4. Watkins PB: The role of cytochromes P-450 in cyclosporine metabolism. J Am Acad Dermatol. 1990 Dec;23(6 Pt 2):1301-9; discussion 1309-11. doi: 10.1016/0190-9622(90)70358-o. [Article]
  5. Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB: PharmGKB summary: cyclosporine and tacrolimus pathways. Pharmacogenet Genomics. 2013 Oct;23(10):563-85. doi: 10.1097/FPC.0b013e328364db84. [Article]
  6. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  7. Flockhart Table of Drug Interactions [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Substrate

Inhibitor

General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Fricker G, Drewe J, Huwyler J, Gutmann H, Beglinger C: Relevance of p-glycoprotein for the enteral absorption of cyclosporin A: in vitro-in vivo correlation. Br J Pharmacol. 1996 Aug;118(7):1841-7. [Article]
  2. Lown KS, Mayo RR, Leichtman AB, Hsiao HL, Turgeon DK, Schmiedlin-Ren P, Brown MB, Guo W, Rossi SJ, Benet LZ, Watkins PB: Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther. 1997 Sep;62(3):248-60. [Article]
  3. Soldner A, Christians U, Susanto M, Wacher VJ, Silverman JA, Benet LZ: Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res. 1999 Apr;16(4):478-85. [Article]
  4. Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB: PharmGKB summary: cyclosporine and tacrolimus pathways. Pharmacogenet Genomics. 2013 Oct;23(10):563-85. doi: 10.1097/FPC.0b013e328364db84. [Article]
  5. Cyclosporine Product Label [Link]
  6. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Substrate

Inhibitor

General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Byrne JA, Strautnieks SS, Mieli-Vergani G, Higgins CF, Linton KJ, Thompson RJ: The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology. 2002 Nov;123(5):1649-58. [Article]
  2. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ: Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology. 2000 Feb;118(2):422-30. [Article]
  3. Zhang J, He K, Cai L, Chen YC, Yang Y, Shi Q, Woolf TF, Ge W, Guo L, Borlak J, Tong W: Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse. Chem Biol Interact. 2016 Aug 5;255:45-54. doi: 10.1016/j.cbi.2016.03.019. Epub 2016 Mar 19. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Inhibitor

General Function
Bile acid:sodium symporter activity
Specific Function
Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism.
Gene Name
SLC10A2
Uniprot ID
Q12908
Uniprot Name
Ileal sodium/bile acid cotransporter
Molecular Weight
37713.405 Da
References
  1. Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA: Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol. 1998 Jan;274(1 Pt 1):G157-69. [Article]
  2. Kosters A, Karpen SJ: Bile acid transporters in health and disease. Xenobiotica. 2008 Jul;38(7-8):1043-71. doi: 10.1080/00498250802040584. [Article]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Inhibitor

General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Schroeder A, Eckhardt U, Stieger B, Tynes R, Schteingart CD, Hofmann AF, Meier PJ, Hagenbuch B: Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol. 1998 Feb;274(2 Pt 1):G370-5. [Article]
  2. Kosters A, Karpen SJ: Bile acid transporters in health and disease. Xenobiotica. 2008 Jul;38(7-8):1043-71. doi: 10.1080/00498250802040584. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Substrate

Inhibitor

General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Sweet DH, Wolff NA, Pritchard JB: Expression cloning and characterization of ROAT1. The basolateral organic anion transporter in rat kidney. J Biol Chem. 1997 Nov 28;272(48):30088-95. [Article]
  2. Taguchi T, Masuo Y, Kogi T, Nakamichi N, Kato Y: Characterization of Long-Lasting Oatp Inhibition by Typical Inhibitor Cyclosporine A and In Vitro-In Vivo Discrepancy in Its Drug Interaction Potential in Rats. J Pharm Sci. 2016 Jul;105(7):2231-9. doi: 10.1016/j.xphs.2016.04.025. Epub 2016 Jun 9. [Article]
  3. Uchida M, Tajima Y, Kakuni M, Kageyama Y, Okada T, Sakurada E, Tateno C, Hayashi R: Organic Anion-Transporting Polypeptide (OATP)-Mediated Drug-Drug Interaction Study between Rosuvastatin and Cyclosporine A in Chimeric Mice with Humanized Liver. Drug Metab Dispos. 2018 Jan;46(1):11-19. doi: 10.1124/dmd.117.075994. Epub 2017 Oct 19. [Article]
  4. Sidharta PN, Treiber A, Dingemanse J: Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan. Clin Pharmacokinet. 2015 May;54(5):457-71. doi: 10.1007/s40262-015-0255-5. [Article]
  5. Novartis Monograph: Apo-Cyclosporine [Link]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Substrate

Inhibitor

Data in the literature is limited regarding this transporter action.
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
Multidrug resistance-associated protein 7
Molecular Weight
161627.375 Da
References
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Inhibitor

General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Hesselink DA, van Hest RM, Mathot RA, Bonthuis F, Weimar W, de Bruin RW, van Gelder T: Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2. Am J Transplant. 2005 May;5(5):987-94. doi: 10.1046/j.1600-6143.2005.00779.x. [Article]
  2. Elamiri A, Perwaiz S, Tuchweber B, Yousef IM: Effect of mdr2 mutation with combined tandem disruption of canalicular glycoprotein transporters by cyclosporine A on bile formation in mice. Pharmacol Res. 2003 Nov;48(5):467-72. doi: 10.1016/s1043-6618(03)00187-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Inhibitor

General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B: Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7. [Article]
  2. Sidharta PN, Treiber A, Dingemanse J: Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan. Clin Pharmacokinet. 2015 May;54(5):457-71. doi: 10.1007/s40262-015-0255-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action

Unknown

Actions

Substrate

Inhibitor

General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Shitara Y, Itoh T, Sato H, Li AP, Sugiyama Y: Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. J Pharmacol Exp Ther. 2003 Feb;304(2):610-6. [Article]
  2. Fehrenbach T, Cui Y, Faulstich H, Keppler D: Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. Naunyn Schmiedebergs Arch Pharmacol. 2003 Nov;368(5):415-20. Epub 2003 Oct 3. [Article]
  3. Gertz M, Cartwright CM, Hobbs MJ, Kenworthy KE, Rowland M, Houston JB, Galetin A: Cyclosporine inhibition of hepatic and intestinal CYP3A4, uptake and efflux transporters: application of PBPK modeling in the assessment of drug-drug interaction potential. Pharm Res. 2013 Mar;30(3):761-80. doi: 10.1007/s11095-012-0918-y. Epub 2012 Nov 22. [Article]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action

No

Actions

Inhibitor

General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Sidharta PN, Treiber A, Dingemanse J: Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan. Clin Pharmacokinet. 2015 May;54(5):457-71. doi: 10.1007/s40262-015-0255-5. [Article]
  2. Shitara Y, Takeuchi K, Nagamatsu Y, Wada S, Sugiyama Y, Horie T: Long-lasting inhibitory effects of cyclosporin A, but not tacrolimus, on OATP1B1- and OATP1B3-mediated uptake. Drug Metab Pharmacokinet. 2012;27(4):368-78. doi: 10.2133/dmpk.dmpk-11-rg-096. Epub 2012 Jan 13. [Article]
  3. Gertz M, Cartwright CM, Hobbs MJ, Kenworthy KE, Rowland M, Houston JB, Galetin A: Cyclosporine inhibition of hepatic and intestinal CYP3A4, uptake and efflux transporters: application of PBPK modeling in the assessment of drug-drug interaction potential. Pharm Res. 2013 Mar;30(3):761-80. doi: 10.1007/s11095-012-0918-y. Epub 2012 Nov 22. [Article]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]

Drug created at June 13, 2005 13:24 / Updated at September 02, 2022 03:30