Interactions of the Hexobarbital Enantiomers with Rat Liver Microsomes

Abstract

There is a stereoselective difference in the interaction of the hexobarbital enantiomers with rat liver microsomes. The metabolism of the hexobarbital isomers was elevated in microsomes isolated from rats pretreated with phenobarbital and the (+)-isomer metabolized to a greater degree in control and phenobarbital-induced preparations. (+)-Hexobarbital was observed to be more effective than the (–)-isomer in the stimulation of endogenous NADPH oxidation and inhibition of ethylmorphine N-demethylation. In binding spectral experiments, the (+)-isomer exhibited larger A_max (maximum absorbance) values and slightly lower apparent Ks (spectral dissociation) constants than the (–)-form in control and phenobarbital-induced microsomal preparations.

Age‐dependent stereoselective increase in the oral clearance of hexobarbitone isomers caused by rifampicin.

“…The metabolism of racemic hexobarbitone has been studied extensively in man (Breimer & Van Rossum, 1973;Breimer et al, 1975a, b;Zilly et al, 1975Zilly et al, , 1978 and animals (Bush & Weller, 1974;Degwitz et al, 1969;Feller & Lubawy, 1973;Furner et al, 1969;McCarthy & Stitzel, 1971;Van der Graaf et al, 1983) and has been shown to be dependent upon the cytochrome P-450 mixed function oxidase system. The 3-hydroxylation of hexobarbitone has been shown to cosegregate with the mephenytoin polymorphism (Knodel et al, 1988).…”