Protease inhibitors Cytochrome P450 isoenzyme substrates

Voriconazole is an inhibitor and a substrate of the cytochrome P450 isoenzyme CYP3A4 protease inhibitors are also metabolised by this route, and can, to varying degrees, also inhibit this isoenzyme. 

Modafinil is an inducer of the cytochrome P450 isoenzyme CYP3A4. The manufacturers therefore predict that it may reduce the levels of drugs that are CYP3A4 substrates. They specifically name the protease inhibitors, buspirone, calcium-channel blockers, ciclosporin, midazolam, and the statins [note that only some statins, namely atorvastatin, lovastatin and... 

Itraconazole is a known substrate and inhibitor of the cytochrome P450 isoenzyme CYP3A4, and the protease inhibitors also inhibit and share this pathway of metabolism. Thus enzyme inhibition, and competition for metabolism results in raised serum levels of both drugs. 

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