Kinetics of misonidazole enantiomers.

The kinetics of misonidazole enantiomers were followed in nine healthy subjects after a single oral dose of racemic misonidazole (1.0 gm/m2). Mean clearance of (+)-misonidazole was 14% greater than that for (-)-misonidazole and mean volume of distribution was slightly greater (3%) for the (+)-enantiomer. After treatment of four of the subjects with cimetidine, there was a small increase in (-)-misonidazole distribution volume, but there was no significant change in other kinetic parameters for either enantiomer. Phenytoin (three subjects) and phenobarbital (two subjects) increased the clearance of both enantiomers (the increase was greater for (+)-misonidazole). The use of (+)-misonidazole together with induction of metabolism may reduce the neurotoxicity associated with racemic misonidazole.