CYP3A4 substrate drugs

In a double-blind, crossover, pharmacokinetic and pharmacodynamic study of the interaction of ketoconazole with alprazolam and triazolam, two CYP3A4 substrate drugs with different kinetic profiles, impaired clearance by ketoconazole had more profound clinical consequences for triazolam than for alprazolam (39). 

Kato, M., Intestinal first-pass metabolism of CYP3A4 substrates. Drug Metab. Pharmaco., 23(2), 87, 2008. 

P Schmeidlin-Ren, DJ Edwards, ME Fitzsimmons, K He, KS Lown, PM Woster, A Rahman, KE Thummel, JM Fisher, PF Hollenberg, PB Watkins. Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab Dispos 25 1228-1233, 1997. 

K. S., Woster, P. M., Rahman, A., Thummei, K. E., Fisher, J., Hollenberg, P. F., Watkins, P. B., Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit juice constituents, Drug Metab. Disp. 1997, 25, 1228-1233. 

Stresser, D.M., Blanchard, A.P., Turner, S.D., Erve, J.C., Dandeneau, A.A., Miller, V.P. and Crespi, C.L. (2000) Substrate-dependent modulation of CYP3A4 catalytic activity analysis of 27 test compounds with four fluorometric substrates. Drug Metabolism and Disposition, 28 (12), 1440-1448. 

Fig. 7.14 Unbound intrinsic clearance of CYP3A4 substrates and relationship with lipophilic-ity. The data has been calculated from various clinical studies with the drugs listed in order of decreasing lipophilicity. 

St. John s wort (H. perforatum) induces CYP3A4. Because drug product is a substrate for CYP3A4, there is the potential that the use of St. John s wort in patients receiving drug product could result in reduced amiodarone levels ... 

There were multiple official regulatory warnings regarding the risk of increased drug levels of CYP3A4 substrates as a result of interactions with... 

Posaconazole is the newest triazole to be licensed in the USA. It is available only in a liquid oral formulation and is used at a dosage of 800 mg/d, divided into two or three doses. Absorption is improved when taken with meals high in fat. Posaconazole is rapidly distributed to the tissues, resulting in high tissue levels but relatively low blood levels. Visual changes have not been reported, but drug interactions with increased levels of CYP3A4 substrates such as tacrolimus and cyclosporine have been documented. 

Delavirdine should not be used in combination with drugs that are CYP3A4 substrates such as pimozide, midazolam, triazolam, amiodarone, propafenone and ergot derivatives. Inducers of the hepatic P-450 system, rifampin, rifabutin, pheno-barbital, phenytoin or carbamazepine, should not be used in combination with delaviridine. It also increases the plasma levels of HIV protease inhibitors. 

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