3540 T3D3498 Cyclosporin A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Cyclosporine is produced as a metabolite by the fungus species Cordyceps militaris. (From Martindale, The Extra Pharmacopoeia, 30th ed). 59865-13-3 6435893 C62H111N11O12 1201.841370 White powder. 148-151°C The absorption of cyclosporine from the gastrointestinal tract is incomplete and variable. The extent of absorption is dependent on the individual patient, the patient population, and the formulation. The absolute bioavailability of cyclosproine administered as Sandimmune&#8482; is dependent on the patient population, estimated to be less than 10% in liver transplant patients and as great as 89% in some renal transplant patients. Compared to an intravenous infusion, the absolute bioavailability of the oral solution is approximately 30% based upon the results in 2 patients. The cyclosporine capsules and oral solution are bioequivalent. The time of peak blood concentrations (Tmax) following oral administration of cyclosporine [modified] ranged from 1.5 - 2.0 hours. Cyclosporine binds to cyclophilin. The complex then inhibits calcineurin which is normally responsible for activating transcription of interleukin 2. Cyclosporine also inhibits lymphokine production and interleukin release. In ophthalmic applications, the precise mechanism of action is not known. Cyclosporine emulsion is thought to act as a partial immunomodulator in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Hepatic, extensively metabolized by the cytochrome P450 3A enzyme system in the liver. It is also metabolized in the gastrointestinal tract and kidney to a lesser degree. The metabolites are significantly less potent than the parent compound. The major metabolites (M1, M9, and M4N) result from oxidation at the 1-beta, 9-gamma, and 4-N-demethylated positions, respectively. Route of Elimination: Elimination is primarily biliary with only 6% of the dose (parent drug and metabolites) excreted in the urine. Only 0.1% of the dose is excreted in the urine as unchanged drug. Half Life: Biphasic and variable, approximately 7 hours (range 7 to 19 hours) in children and approximately 19 hours (range 10 to 27 hours) in adults. The oral LD<sub>50</sub> is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The I.V. LD<sub>50</sub> is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits. 1, carcinogenic to humans. (L135) For treatment of transplant (kidney, liver, and heart) rejection, rheumatoid arthritis, severe psoriasis. The oral LD<sub>50</sub> is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The I.V. LD<sub>50</sub> is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits. 2009-07-30T17:58:49Z 2014-12-24T20:26:07Z Cyclosporine C05086 4031 Cyclosporin DB00091 true [H]\C(C)=C(\[H])CC(C)C(O)C1N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)N=C(O)C(C)N=C(O)C(CC(C)C)N(C)C(=O)C(N=C(O)C(CC(C)C)N(C)C(=O)CN(C)C(=O)C(CC)N=C1O)C(C)C C62H111N11O12 InChI=1/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+ InChIKey=PMATZTZNYRCHOR-IMVLJIQENA-N 1202.6112 1201.841368071 Exogenous Solid CHEMBL160 <p>Hans Dietl, &#8220;Pharmaceutical preparation containing cyclosporine(s) for intravenous administration and a process for its production.&#8221; U.S. Patent US5527537, issued October, 1990.</p>