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/mm/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 farms of cytochrome “P-450” mediate the metabolism of C in the rabbit.
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This work was supported in part by grant HD 16900 from the National Institutes of Health.
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Dorrbecker, S.H., Ferraina, R.A., Dorrbecker, B.R. et al. Caffeine and paraxanthine pharmacokinetics in the rabbit: Concentration and product inhibition effects. Journal of Pharmacokinetics and Biopharmaceutics 15, 117–132 (1987). https://doi.org/10.1007/BF01062339
- product inhibition
- nonlinear pharmacokinetics