TABLE 4

Efavirenz metabolism using preinduced HepatoPac with 14C-efavirenz

14C-Efavirenz Percent Change Relative to Solvent Controla
CYP3A4/CYP2B6 InducerCYP2B6 InhibitorCYP3A4 InhibitorCYP2A6 InhibitorPan-UGT Inhibitor
CBZEFVRIFTICERYPCPAHTEL
8-OH and its glucuronide conjugate+60−17−22−76−54+16−16
7-OH and its glucuronide conjugate−26−33−37+88−22−94+48
N-Glucuronide−60−37−60−59−54−79−98
EFV−52+17+19+40+47+13+7
  • Human hepatocytes using HepatoPac cells were initially induced with 10 µM [14C]-efavirenz for 96–120 hours (total radioactivity recovered ranged between 9.7 and 10.4 µM). Induced human HepatoPac plates were then incubated with and without inducers for an additional 72 hours (10 µM RIF, 10 µM EFV, and 100 µM CBZ) or were coincubated with inhibitors (50 µM ERY, 10 µM TIC, 10 µM TEL, and 10 µM PCPAH). CBZ, carbamazepine; EFV, efavirenz; ERY, erythromycin; RIF, rifampin; TEL, telmisartan; TIC, ticlopidine.

  • a Percent change relative to the solvent control is calculated as = 100 − (concentration in presence of inhibitor or inducer/concentration in solvent control × 100). Plus signs indicate an increase in concentration relative to the solvent control and minus signs indicate a decrease in concentration relative to the solvent control.