Inter- and intrasubject variations of ranitidine pharmacokinetics after oral administration to normal male subjects

Abstract

Inter- and intrasubject variations of ranitidine pharmacokinetics were examined following oral administration of ranitidine tablets (150 mg as base) under controlled conditions at a timed interval of one week (periods I and II) to 12 healthy male subjects. Significant secondary peaks in the plasma concentration-time curves were observed in all subjects in both periods. The first peak occurred at 0.5 to 2.5 h and the second peak at 3 to 6 h after the dosing. There were great variations in the plasma concentration-time profiles among subjects; for example, the area under the plasma concentration-time curve from time 0 to 12 h (AUC0-12) varied from 1905 to 5672 micrograms.h/mL. But bioavailability parameters of period I, such as maximum concentration of the first and second plasma peak (Cmax 1 and Cmax 2, respectively), time to first peak (tmax 1), AUC0-12, and AUC from time zero to infinity (AUC0-infinity), were correlated significantly with those of period II. These results suggest that the intrasubject variation of ranitidine pharmacokinetics is usually small over at least one week under the controlled conditions of this study, in spite of its great intersubject variation.