Fig 10.

Schematic summarizing the phase I and phase II metabolism of RPV. Monohydroxylated metabolites, M1 and M2, and dihydroxylated metabolites, M3 and M4, result from oxygenation of RPV by CYP3A4 and CYP3A5. M5 results from direct glucuronic acid conjugation to RPV by UGT1A4. M6 results from glucuronidation of monooxygenated metabolite M1 by UGT1A1, and M7 results from glucuronidation of dioxygenated metabolite M4; however, the UGT responsible for this conjugation was unable to be determined from our studies.