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.
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Department of Pharmacy Practice, Ferris State University College of Pharmacy, Lansing, MI, USA. curtis_smith@ferris.edu
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D000818:Animals; D019540:Area Under Curve; D002110:Caffeine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005508:Food Deprivation / Q000502:physiology*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D014970:Xanthines; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2