Ranitidine disposition and systemic availability in hepatic cirrhosis

Single-dose ranitidine kinetics were studied in 10 patients with cirrhosis as proved by liver biopsy. All were clinically stable. After an overnight fast, ranitidine was given in a randomized crossover order as a bolus intravenous injection (50 mg) or was taken by mouth (150 mg). Terminal t 1 2 was 2.7 ± 0.4 hr after oral dosing and 2.9 ± 0.4 hr after intravenous injection. Total plasma clearance was 470 ± 170 ml/min and the steady-state volume of distribution was 1.2 ± 0.2 l/kg. There was considerable intersubject variability in the ranitidine serum concentration-time profile after oral dosing. Systemic availability as assessed by AUC analysis was 58% ± 11 %. Not all of the dose could be recovered in the urine as unchanged ranitidine and its known metabolites after intravenous injection. At 0.5 μg/ml the serum protein binding of ranitidine was 4.6% ± 1.3%. It is concluded that disposition of ranitidine in these 10 stable subjects with cirrhosis was not significantly altered. The minor changes observed in some were as likely to be the result of secondary perturbations in physiologic status as to effects of cirrhosis on drug metabolism.