SPECIES-RELATED DIFFERENCES IN THE STEREOSELECTIVE GLUCURONIDATION OF OXAZEPAM

  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (6) , 605-608
Abstract
The concentrations of (R)-(-)- and (S)-(+)-oxazepam glucuronides in plasma and urine of several species [rabbit, monkey, dog, swine, man] were measured. The relative amounts of these diastereoisomers vary among species. In the plasma and urine of rhesus monkeys [Macaca mulatta] 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 2 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. 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.