PHARMACOKINETIC DIFFERENCES OF DESMETHYLDIAZEPAM IN 3 OUTBRED WISTAR STRAINS RELATED TO DIFFERENCES IN LIVER-ENZYME ACTIVITIES

Various strains of rats differ in their sensitivities towards benzodia zepines suggesting that variations in biological features are responsi ble for these differences. All reports concern inbred strains. We have studied male rats of three outbred Wistar strains with regard to the pharmacokinetics of desmethyldiazepam given as a single intravenous do se. The elimination half-life of desmethyldiazepam was longer in the R iv:TOX(M) (from the National Institute of Public Health and Environmen tal Protection) and in the Cpb:WU strain than in the Crl:(WI)BR strain . This strain difference in elimination of desmethyldiazepam may be re lated to differences in liver enzyme activities.