Systemic clearance and demethylation of caffeine in sheep and cattle

Pharmacokinetics of caffeine have been studied in sheep and cattle treated with caffeine (5 mg/kg) by intravenous injection. Terminal-phase elimination half-lives were 8.9 hr in sheep and 8.1 hr in cattle. Noncompartmental analyses of data collected from individual animals indicate that neither terminal-phase rate constants (beta) nor mean residence times of caffeine in plasma differed between species. Each of the three possible N-demethylated primary metabolites of caffeine was detected in plasma from each species, with theophylline predominating in sheep and paraxanthine predominating in cattle. These data indicate that hepatic capacity to clear caffeine from the systemic circulation is similar between sheep and cattle, but that the preferred routes of metabolism differ. Expression of cytochromes P4501A (CYP1A subfamily) may differ between these species.