Nonlinear pharmacokinetics of aspirin in rats.

摘要: Rats are frequently used as an animal model for studies of the antithrombotic action aspirin. The purpose this investigation was to explore factors that influence systemic exposure unhydrolyzed aspirin after oral and administration drug adult male Sprague-Dawley rats. experiments were performed according a crossover design, concentration measurements made on whole blood. Intravenous injection (200 mg/kg) showed is eliminated rapidly (total clearance approximately 45 ml/min/kg; half-life 8 min), only about one-fourth dose absorbed intact, availability highly variable (coefficient variation 60%). A 40 mg/kg i.v. cleared almost twice 200 dose. Injection salicylic acid yield concentrations similar those obtained large (approximately 400 mg/l) reduced total by one-third, suggesting product inhibition ester hydrolysis. infused into portal circulation 80% over wide range infusion rates, showing presystemic hydrolysis occurs mainly in gut. As humans, absorption orally administered affects exponential decline blood, resulting apparent substantially longer than actual biologic injection.(ABSTRACT TRUNCATED AT 250 WORDS)