The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration

We have studied the pharmacokinetics of ranitidine, a new H2-receptor blocker in 6 male patients suffering from chronic duodenal ulceration. In 5 patients single-dose kinetics were determined over a 24-hour period following 150 mg of ranitidine given orally and steady state kinetics were examined after treatment for 28 days with 150 mg ranitidine given twice daily. At this stage all 5 patients showed endoscopic evidence of ulcer healing. Our findings showed little inter-individual variation in elimination half-life, peak level, trough level and area under the curve (AUC). Significant differences were found between single dose and steady state situations with respect to the elimination half-life (p less than 0.01), peak levels (p less than 0.01) and area under the curve (p less than 0.05), and no differences in trough levels. The higher peak levels and larger AUC indicate increased bioavailability in steady state. The elimination half-life was shorter in steady state. The steady state kinetics of the sixth patient, a male aged 54 years, with a history of alcohol abuse and chronic duodenal ulceration who had failed to respond symptomatically to treatment with 150 mg ranitidine given twice daily for 8 weeks showed a reduction of peak level and AUC, both of which were corrected over 2 weeks by doubling the daily dose of ranitidine. The initial failure of response of this patient was likely to have been due to pharmacokinetic factors.