| Abstract: | Latamoxef (daily 100 and 300 mg/kg, i.v.) was injected once a day for 8 days to 75% and 90% nephrectomized rats kept on a vitamin K-sufficient diet (500-600 ng/g) or a vitamin K-deficient diet (30-50 ng/g), and changes in ADP-induced platelet aggregation and prothrombin time were examined. The half-life of latamoxef was markedly prolonged and plasma latamoxef and N-methyltetrazolethiol (NMTT) concentrations increased, resulting in a delay of the total body clearance of the compounds. The ADP-induced platelet aggregation increased after nephrectomy, and latamoxef slightly but inconsistently decreased the aggregation. Prothrombin time did not change even in the 90% nephrectomized rats kept on an ordinary diet, but increased dose-dependently in the vitamin K-deficient nephrectomized rats, with the 90% nephrectomized animals showing larger increases of prothrombin time. These data suggest that NMTT or NMTT-containing antibiotics cause no hypoprothrombinemia even in partially nephrectomized rats when they are fed an ordinary diet containing vitamin K, but these compounds enhance the manifestation of hypoprothrombinemia in vitamin K deficiency. Further renal failure promotes the manifestation by increasing drug concentration in the blood. However, platelet aggregation in these animals is not significantly affected at the doses examined. |
