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. 1987 Apr;15(2):117-32.
doi: 10.1007/BF01062339.

Caffeine and paraxanthine pharmacokinetics in the rabbit: concentration and product inhibition effects

S H Dorrbecker, R A Ferraina, B R Dorrbecker, P A Kramer

Caffeine and paraxanthine pharmacokinetics in the rabbit: concentration and product inhibition effects

S H Dorrbecker et al. J Pharmacokinet Biopharm. 1987 Apr.

Abstract

The disposition of caffeine (C) and its major metabolite paraxanthine (P) have been determined following i.v. bolus dosing both separately and concomitantly to New Zealand White rabbits. Caffeine clearances of 1.52-6.71 ml/min/kg were observed and were suggestive of polymorphism with rapid (type I) and slow (type II) metabolizing subpopulations represented. Type II metabolizers exhibited dose-independent pharmacokinetics for C, while the clearances of type I animals were dose-dependent (lower clearances at higher doses). The P clearances were not dose-dependent. In type I rabbits coadministration of P inhibited C metabolism by as much as 71%. Results were consistent with the hypothesis that at least two forms of cytochrome "P-450" mediate the metabolism of C in the rabbit.

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