14C-Efavirenz Percent Change Relative to Solvent Controla | |||||||
---|---|---|---|---|---|---|---|
CYP3A4/CYP2B6 Inducer | CYP2B6 Inhibitor | CYP3A4 Inhibitor | CYP2A6 Inhibitor | Pan-UGT Inhibitor | |||
CBZ | EFV | RIF | TIC | ERY | PCPAH | TEL | |
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.