Species-related differences in the stereoselective glucuronidation of oxazepam.

The concentrations of (R)-(-)- and (S)-(+)-oxazepam glucuronides in plasma and urine of several species have been measured. The relative amounts of these diastereoisomers vary among species. Thus, in the plasma and urine of rhesus monkeys the concentrations of the R-isomer are higher, whereas in man and dog more of the S-isomer is present. In plasma and urine of miniature swine the amounts of the two diastereoisomers are about equal. In the urine of rabbits the S-isomer prevails. Similar species-related differences are observed in the in vitro formation of the isomeric oxazepam glucuronides. Homogenates of dog, miniature swine, rabbit, and rat liver produce more of the S-isomer, whereas with monkey liver the formation of (R)-oxazepam glucuronide is favored. The agreement between in vivo and in vitro data is fairly good for rhesus monkey, miniature swine, and rabbit. However, for the dog the ratio of S- to R-isomers in the liver homogenate is much higher than in plasma and urine. This species-dependent stereoselective glucuronidation of oxazepam is not related to the phylogenetic or dietary grouping of these species.