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Comparison of bioavailability (BA) of three brands of ranitidine (RT) tablets has been studied in rats. The purpose of this study was to characterize the pharmacokinetics of RT tablets in the rat and to compare pharmacokinetic parameters of three brands of RT tablets. In addition, it was investigated whether plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats. RT was administered intravenously in dose of RT-HCl 10mg/kg and orally in dose of RT-HCl 50mg/kg as solution or crushed sample of tablets. Plasma RT concentrations were determined by HPLC. RT concentrations as a function of time were fitted to two compartment model. Plasma RT concentrations declined with a terminal half life (t1/2beta) of 40.9 min. The plasma RT concentration-time curve showed two peak plasma concentrations following an oral administration of solution or crushed sample in rats like humans. No significant difference among pharmacokinetic parameters was observed except Tmax2 (p<0.05). In compared with BA of three crushed samples, Cmax1 was showed significant difference between crushed sample A and B (pmax2 was showed significant difference between crushed sample A and C (p<0.05). The BA for crushed sample A, B and C were found to be 54.6, 40.7 and 40.0%, respectively. Equivalence of Cmax1 and Tmax2 were guaranteed in this study. However. it was concluded that three brands of RT tablets are bioequivalent, taking the following characteristics of RT into consideration; (1) rapid onset of the effect is not required, (2) Cmax1 and Tmax2 do not seem to influence the effectiveness of the drug during a long-term treatment by the usual administration of twice a day. Results from this study were combined with pharmacokinetic data for RT in dogs and humans to develop a basis for interspecies scale-up of the disposition characteristics of the drug. There were similarities in the general disposition of the drug. Allometric relationships were sought between pharmacokinetic parameters and species body weight. Significant interspecies correlations were found for total body clearance (Clt) and steady state volume of distribution (Vdss). Thus, plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats.
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