Pharmacokinetics of Ranitidine Following Oral Administration With Ascending Doses and With Multiple‐Fixed Doses

Abstract

The aim of these studies was to further delineate pharmacokinetic characteristics of ranitidine, a new histamine H₂‐receptor antagonist In one study, ranitidine was administered orally to six normal men in increasing doses of 100 mg, 150 mg, 250 mg, and 400 mg weekly over a four‐week period. The peak serum concentrations increased with the corresponding increases in dose but the time needed to reach peak serum concentration did not vary significantly with increased doses. The pharmacokinetic parameters were calculated for each subject at each of the four dose levels. The total area under the curve (AUC) at the four different doses was linearly related to the dose for each individual subject; and a plot of AUC versus dose had a correlation coefficient of .886 (P < .001). The apparent plasma clearance did not vary with the increase in dose; and the average corrected clearance values ranged between 6.7 and 10 mL/(min × kg). Elimination half‐life was between 2.6 and 3.0 hours; and the volume of distribution (Vd area) was between 1.6 and 2.4 L/kg. About 35% of the ranitidine dose was excreted in the urine in the unchanged form over a 12‐hour excretion interval. In the second study, ranitidine was administered orally to 12 normal subjects in doses of 150 mg and 200 mg twice daily for 28 days. The pharmacokinetic parameters for ranitidine with multiple‐dose treatment were similar to those obtained with single‐dose administration. Predose ranitidine concentrations (trough levels) did not increase with multiple dose administration. These studies indicate that the pharmacokinetics of ranitidine are linear in the dose range of 100 mg to 400 mg, and were similar with both single‐ and multiple‐dose administrations.