Use of single sample clearance estimates of cytochrome P450 substrates to characterize human hepatic CYP status in vivo.

1. Single sample clearance estimates (CL/F) of orally administered ethosuximide were obtained in four groups of healthy adult subjects. One group was treated with phenobarbital to induce CYP2B/2C and CYP3A activity; one group was treated with rifampin to induce CYP3A activity; one group consisted of cigarette smokers (increased CYP1A activity), and one group was untreated (controls). Ethosuximide CL/F values were slightly, though not significantly, increased among cigarette smokers (12.5% increase) and the phenobarbital group (25% increase), but rifampin treatment resulted in a significant increase (65%). 2. The influence of rifampin treatment on the single sample oral clearances of antipyrine, theophylline, phenytoin, carbamazepine, ethosuximide, quinidine, valproic acid, and lorazepam was investigated to determine whether rifampin induces only CYP3A. Rifampin treatment significantly increased the oral clearance of each drug from 1.4-fold (valproic acid) to 3.4-fold (quinidine). These findings indicate that the inductive effect of rifampin extends well beyond CYP3A.