Ketoconazole inhibition

Ketoconazole inhibits a variety of cytochrome P450 enzymes, including 11-hydroxylase and 17-hydroxylase. It is highly effective in lowering cortisol in Cushing s disease, and patients can be maintained successfully on therapy for months to years. The most common adverse effects are reversible elevation of hepatic transaminases and GI upset. It can cause gynecomastia and lower plasma testosterone values. 

B. Finasteride is a 5a-reductase inhibitor, which essentially makes dihydrotestosterone unavailable to the prostate but does not reduce serum testosterone levels. The decreased prostatic levels of dihydrotestosterone frequently result in a size regression of the prostate, while the relatively normal testosterone levels minimize a depressed libido. Flutamide and spironolactone exhibit antiandrogen effects by competing for the androgen receptor ketoconazole inhibits testosterone synthesis and stanozolol is an oral anabolic androgen preparation. 

Greenblatt, D.J., Wright, C.E., von Moltke, L.L., Harmatz, J.S., Eh-renberg, B.L., Harrel, L.M., Corbett, K., Counihan, M., Tobias, S., and Shader, R.I. (1998) Ketoconazole inhibition of triazoloam and alprazolam clearance differential kinetic and dynamic consequences. Clin Pharmacol Ther 64 237-247. 

Susceptible to enzyme inducers (itraconazole, ketoconazole, voriconazole). Gastrointestinal absorption pH-dependent (itraconazole, ketoconazole). Inhibition of P-glycoprotein (itraconazole, ketoconazole, posaconazole). 

Mechanism of Action. Fluconazole and similar agents (itraconazole, ketoconazole) inhibit certain enzymes in fungal cells that are responsible for the synthesis of important sterols.9,15 A deficiency of these... 

Greenblatt DJ, Wright CE, von Moltke LL, et al. Ketoconazole inhibition of triazolam and alprazolam clearance differential kinetic and dynamic consequences. Clin Pharmacol Ther 1998 64 237-247. 

D. Ketoconazole inhibits cytochrome P-450 enzymes that inactivate cyclosporine. 

The correct answer = D. Ketoconazole is effective against Candida, but it does not react with cyclosporine nor is it cardiotoxic. Ketoconazole inhibits the hepatic cytochrome P-450 enzymes that inactivate cyclosporine. Thus in this instance the patient would be in danger of increased cyclosporine toxicity. Though ketoconazole does cause gynecomastia and decreased libido, this would not be of primary concern. 

Herman BD, Fleishaker JC, Brown MT. Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in humans. Clin Pharmacol Ther 1999 66(4) 374-9. 

Ketoconazole inhibits a variety of cytochrome P450 enzymes, including... 

RIMONABANT ANTIFUNGALS- KETOCONAZOLE t rimonabant levels Ketoconazole inhibits CYP3A4-mediated metabolism of rimonabant Avoid co-administration... 

ITRACONAZOLE, KETOCONAZOLE PROTEASE INHIBITORS Possibly t levels of ketoconazole by amprenavir, indinavir and ritonavir (with or without lopinavir). Conversely, indinavir, ritonavir and saquinavir levels t by itraconazole and ketoconazole Inhibition of, or competition for, CYP3A4-mediated metabolism Use itraconazole with caution and monitor for adverse effects. No dose adjustment is recommended for doses <400 mg/day of ketoconazole... 

Donepezil Ketoconazole Inhibited metabolism of donepezil Monitor for donepezil toxicity dose reduction not empirically necessary... 

The fact that ketoconazole inhibits cytochrome P450 accounts for some of its interactions. Ketoconazole increases ciclosporin concentrations, enhancing the risk of renal impairment, as shown by a fall in creatinine clearance (SED-12, 678) (6,13,25,36). 

Brynne N, Forslund C, Hallen B, Gustafsson LL, Bertilsson L. Ketoconazole inhibits the metabolism of tol-terodine in subjects with deficient CYP2D6 activity. Br J Clin Pharmacol 1999 48(4) 564-72. 

Fleishaker JC, Herman BD, Pearsotr LK, lorrita A, Mucci M. Evaluation of the potential pharmacokinetic/pharmaco-dynamic interaction between fluoxetine and reboxetine in healthy volunteers. Clin Drug Invest 1999 18 141-50. Herman BD, Fleishaker 1C, Brown MT. Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in humans. Clin Pharmacol Ther 1999 66(4) 374-9. 

Ketoconazole—inhibits CYPl7 enzymes (17a-hydroxylase and Ci7,2o-lyase), particularly those involved in testosterone synthesis. After 6 months of treatment in hirsute women, serum testosterone declines without a change in serum cortisol or DHEAS. 

Treatment Fluconazole, itraconazole, ketoconazole Inhibit P450 3A4 monitor CSA and TAC levels decrease... 

May cause mild CNS and GI effects and 1 bioavailability of drugs that require acidity for oral absorption (e.g., fluoroquinolones, ketoconazole). Inhibit P450 — >L elimination of diazepam, phenytoin, and warfarin. 

Van Wauwe, J.P., Coene, M.C., Goossens, J., Van Nijen, G., Cools, W. and Lauwers, W. (1988) Ketoconazole inhibits the in vitro and in vivo metabolism of ull-trans-retinoic acid. The Journal of Pharmacology and Experimental Therapeutics, 245, 718-722. 

Inhibitors of P450 17A1 have been studied for some time. Interestingly, ketoconazole inhibits lyase activity but not 17-hydroxylation activity7a-Thiospirolactone is a mechanism-based inhibitor of (guinea pig) P450 17A1 (ref [1273]). 

Ketoconazole inhibits many types of cytochrome P450 enzymes. It can be used to reduce the unregulated overproduction of corticosteroids by adrenal tumors. The answer is (D). 

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