Cyclosporine cytochrome

Clinically important, potentially hazardous interactions with aluminium hydroxide, antacids, charcoal, cholestyramine, colestimide, colestipol, cyclosporine, cytochrome P4503A substrates, dapsone, estrogenic hormones, nitrendipine, oral contraceptives... 

Oral azoles are associated with significant interactions, particularly due to cytochrome P-450 isoenzymes. Medications that interact with azoles include warfarin, phenytoin, theophylline, rifampin, cyclosporine, and zidovudine. For patients receiving only a few doses, these interactions do not pose a significant risk. These interactions may pose a risk for patients receiving long-term suppressive therapy for recurrent infections. 

The answer is b. (Katzungr pp 806—807J Rifampin induces cytochrome P450 enzymes, which causes a significant increase in elimination of drugs, such as oral contraceptives, anticoagulants, ketoconazole, cyclosporine, and chloramphenicol. It also promotes urinary excretion of methadone, which may precipitate withdrawal. 

Ahmed, S.S., Napoli, K.L. and Strobel, H. W. (1995) Oxygen radical formation during cytochrome P450-catalyzed cyclosporine metabolism in rat and human liver microsomes at varying hydrogen ion concentrations. Molecular and Cellular Biochemistry, 151 (2),... 

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

A4 inhibitors - Patients receiving cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (erythromycin and clarithromycin), antifungal agents (ketoconazole, itraconazole, and miconazole), or cyclosporine or vinblastine should not receive doses of tolterodine greater than 1 mg twice/day (greater than 2 mg/day for ER capsules). 

Metabolism - Cyclosporine is metabolized by the cytochrome P-450 3A4 hepatic enzyme system. 

P-450 system Monitoring of circulating cyclosporine levels and appropriate dosage adjustment are essential when drugs that affect hepatic microsomal enzymes, particularly the cytochrome P-450 3A enzymes, are used concomitantly (eg, HIV protease inhibitors, anticonvulsants, azole antifungals). 

Pichard, L., Domergue, J., Fourtanier, G., Koch, P., Schran, H. F., and Maurel, P. (1996) Metabolism of the new immunosuppressor cyclosporin G by human liver cytochromes P450. Biochem. Pharmacol. 51, 591-598. 

Rifampicin is a potent inducer of cytochrome P450 enzymes and thus can diminish the activity of a multitude of other agents such as warfarin, gluco-corticosteroids, cyclosporin, oral contraceptives and sulphonylurea-type oral antidiabetic agents. 

Absorption after oral administration is incomplete and variable. Its bioavailability ranges from 20% to 50%. Cyclosporine can also be given intravenously. Plasma protein binding is about 90% and cyclosporine also accumulates in red blood cells. It is extensively metabolized in the gastrointestinal mucosa and in the liver by the cytochrome P450-enzyme system. Its elimination half-life is about 19 hours in adults with a range of 10-27 hours and about 9 hours in children with a range of 3-19 hours. Over 30 different metabolites have been... 

Answer Cyclosporine is an immunosuppressant drug used to prevent transplant rejections. Though an oral formulation is available, it has low bioavailability (very httle reaches the systemic circulation as intact drug). Diltiazem will inhibit cytochrome P450 3A4 in the gut. CYP3A4 is the... 

Cyclosporin, tacrolimus Probable induction of cytochrome P450 metabolic pathway Reduced blood levels Risk of rejection of transplant Monitor cyclosporine levels and stop SJW Readjust dose of cyclosporine if required... 

Greenblatt DJ, von Moltke LL, Harmatz JS, et al Human cytochromes and some newer antidepressants kinetics, metabolism, and drug interactions. J Clin Psychopharmacol 19 23S-35S, 1999 Karliova M, Treichel U, Malago M, et al Interaction of Hypericum perforatum (St. John s wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 33 853-855, 2000 Michalets EL Update clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 18 84-112, 1998... 

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