USE OF SINGLE SAMPLE CLEARANCE ESTIMATES OF CYTOCHROME-P450 SUBSTRATES TO CHARACTERIZE HUMAN HEPATIC CYP STATUS INVIVO

1, Single sample clearance estimates (CL/F) of orally administered eth osuximide were obtained in four groups of healthy adult subjects. One group was treated with phenobarbital to induce CYP2B/2C and CYP3A acti vity; one group was treated with rifampin to induce CYP3A activity; on e group consisted of cigarette smokers (increased CYP1A activity), and one group was untreated (controls). Ethosuximide CL/F values were sli ghtly, 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 antipyri ne, theophylline, phenytoin, carbamazepine, ethosuximide, quinidine, v alproic acid, and lorazepam was investigated to determine whether rifa mpin induces only CYP3A. Rifampin treatment significantly increased th e oral clearance of each drug from 1-4-fold (valproic acid) to 3-4-fol d (quinidine). These findings indicate that the inductive effect of ri fampin extends well beyond CYP3A.