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

Abstract Pseudoracemic hexobarbital (HB), consisting of equal molar fractions of 5 (+) HB and deuterium-labeled R (−) HB, d 3 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 5 (+) HB and d 3 R (−) HB were correlated in untreated rats, and in rats pretreated with 3-methylcholanthrene (MC), carbon tetrachloride (CCl 4 ), and different doses of phenobarbital (PB). Although in the different groups some variation in the clearance ratio of 5 (+) HB over d 3 R (−) HB was found, the clearance of 5 (+) HB was generally up to a factor of five higher than the clearance of d 3 R (−) HB, except for the CCl 4 -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.