PHARMACOKINETICS OF A NOVEL BENZODIAZEPINE PARTIAL INVERSE AGONIST INTHE F344 RAT, SD RAT AND B6C3F1 MOUSE

1. The pharmacokinetics of a novel benzodiazepine partial inverse agon ist (S-8510) were studied in the Fischer 344 (F344) rat and B6C3F1 mou se to obtain information for the planning of carcinogenicity studies. Sprague-Dawley (SD) rats were also included for comparison. 2. Clear n on-linear elimination of S-8510 was observed after single oral adminis tration of S-8510 in all animals tested (F344 rat, 1-50 mg/kg; SD rat and B6C3F1 mouse, 1-150 mg/kg). 3. Exposure of S-8510 after single ora l administration was in the order F344 rat > B6C3F1 mouse > SD rat. 4. Multiple oral administration to F344 rat and B6C3F1 mouse decreased t he exposure to S-8510. 5. These results indicate that it is very impor tant to evaluate pharmacological and toxicological studies based on ex posure and to be careful in selecting the species and strains of anima l used in toxicology studies.