Correlation of apparent intrinsic clearances of simultaneously administered S (+) and d3R (-) hexobarbital in the rat

Pseudoracemic hexobarbital (HB), consisting of equal molar fractions of S (+) HB and deuterium-labeled R (-) HB, d3 R (-) HB, was administered orally to rats in a dose of 50 mg/kg. Concentrations of both enantiomers in blood were measured by an enantioselective mass fragmentographic assay. Clearance data of S (+) HB and d3 R (-) HB were correlated in untreated rats, and in rats pretreated with 3-methylcholanthrene (MC), carbon tetrachloride (CCl4), and different doses of phenobarbital (PB). Although in the different groups some variation in the clearance ratio of S (+) HB over d3 R (-) HB was found, the clearance of S (+) HB was generally up to a factor of five higher than the clearance of d3 R (-) HB, except for the CCl4-treated rats. From the present data it can be tentatively concluded that S (+) HB and R (-) HB are metabolized by similar (PB-inducible) cytochrome P-450s in control and PB- and MC-pretreated rats and that clearance data obtained with racemic HB following different pretreatments may be employed as a reflection of (PB-inducible) cytochrome P-450 activity.