In vitro reaction phenotyping studies on rifamycins to explain the auto-induction of rifabutin metabolism.

A study was carried out to establish the relative contribution of human cytochrome P450 (CYP450) enzymes in the metabolism of rifampicin (RMP), rifapentine (RPT) and rifabutin (RFB). It involved the incubation of the three drugs in five major CYP450 isoforms. Both RMP and RPT showed minimal metabolism by CYP450 enzymes, whereas RFB showed extensive metabolic degradation by CYP3A4. A known inducer of CYP3A4, RFB was shown in this study to be also a substrate for the same enzyme. The latter might be one of the reasons for the auto-induction of RFB metabolism and the consequent lower bioavailability of the drug on repeated administration.