Thiamine whole blood and urinary pharmacokinetics in rats: urethan-induced dose-dependent pharmacokinetics

The whole blood pharmacokinetics of thiamine after intravenous administration of thiamine hydrochloride (4, 12, and 36 mg/kg) to rats anesthetized continuously with ether (inhalation) or urethan (1 g/kg ip) were studied. Urinary excretion of thiamine after intravenous administration of thiamine hydrochloride to rats lightly anesthetized with ether was also investigated. At any particular dose, thiamine displayed apparent classical two-compartment model behavior in the time range studied. Under urethan anesthesia, thiamine displayed apparent dose-dependent kinetics as measured by the changes in the pharmacokinetic parameters, AUC,Vd(area), t0.5 beta, and total body clearance, ClTB, with dose. However, when ether anesthesia was used, thiamine displayed dose-independent pharmacokinetic behavior. These results suggest that care should be taken in the interpretation of pharmacokinetic data obtained in anesthetized animals, particularly when urethan anesthesia is used.