Dose Independent Pharmacokinetics of Caffeine after Intravenous Administration under a Chronic Food-limited Regimen

Several studies have shown that caffeine follows non-linear pharmacokinetics in both rats and humans. Recent data have demonstrated that caffeine may following linear pharmacokinetics when administered orally and intraperitoneally to food-limited rats. In this study the pharmacokinetics of caffeine was analyzed following intravenous (i.v.) administration to rats under a food-limited regimen. Four rats were administered four doses of caffeine and a standard dose of the caffeine metabolites, paraxanthine, theobromine, and theophylline. Caffeine pharmacokinetic parameters were dose independent following intravenous doses ranging from 1 to 20 mg/kg. Furthermore, the caffeine area under the curve (AUC) increased linearly as a function of dose. The mean fraction of caffeine converted to paraxanthine, theobromine, and theophylline was 16%, 16%, and 7%, respectively. The linear pharmacokinetics demonstrated in the present study may be attributed to the induction of hepatic metabolism under a chronic food-limited regimen.