Pharmacokinetics of Ranitidine in Patients With Renal Failure

Abstract

The pharmacokinetics of ranitidine were studied in ten patients with renal failure (creatinine clearance, 6–54 mL/min) after intravenous (IV) (50 mg) and oral doses (150 mg). After oral administration, peak plasma concentrations of 378–808 ng/mL were obtained in two to six hours. Plasma concentrations declined very slowly and concentrations greater than 100 ng/mL were obtained for 16 to 20 hours after the dose. The elimination half‐life following oral administration was 8.5 ± 2.8 hours (standard deviation [SD]), and the bioavailability of ranitidine was 43.3% ± 10.5%. After IV administration, the elimination half‐life, plasma clearance, renal clearance, and volume of distribution were 7.0 ± 1.0 hours, 170 ± 38 mL/min, 36.0 ± 25.0 mL/min, and 1.3 ± 0.4 L/kg, respectively. About 20% of the IV dose and 9% of the oral dose were recovered unchanged in urine. There was a significant correlation between the renal clearance of ranitidine and creatinine clearance (r = .74, P < .05) after IV administration. The elimination half‐life in patients with renal insufficiency is about three times greater than that reported in the literature for healthy subjects. Similarly, the plasma clearance in these patients is about 20% of that reported in healthy subjects. The results indicate that ranitidine elimination is appreciably reduced in renal failure and that an adjustment of dose in patients with renal failure is warranted. A dose of 75 mg bid may be adequate in maintaining the therapeutic plasma concentrations that are required for adequate H₂‐blocking activity.