SEX-DIFFERENCES IN THE METABOLISM OF (-S-145, A NOVEL THROMBOXANE A(2) RECEPTOR ANTAGONIST IN RAT())

1. After the oral administration of 5 mg/kg 5-1452 to rat, the plasma levels of (+)-S-145 were similar between the male and female, but ther e were sex differences in the profiles of its beta-oxidized and hydrox ylated metabolites in plasma. 2. beta-Oxidation of(+)-S-145 determined in vitro was slightly higher in the female than in the male, and agre ed with the plasma levels of the beta-oxidized metabolites. 3. 5-Hydro xylation activities of (+)-S-145 and beta-oxidized metabolites by rat liver microsomes were significantly higher in the male than in the fem ale, but marked sex differences were not observed in 6-hydroxylation a ctivities. These results revealed that differences in monooxygenase ac tivities directly account for the sex differences in the plasma level of 5-hydroxylated metabolites, and that the peroxisomal beta-oxidation enzyme system also affected the plasma level of 6-hydroxylated metabo lites. 4. Biliary excretion was higher in the male than in the female, and quantitative identification of metabolites in bile indicated that this was based on the prominent excretion of taurine conjugates in th e male rat. This conclusion was supported by the fact that taurine con jugation activity was higher in male liver homogenates than in the fem ale.