Dosage Regimen for Ranitidin in Renal Impairment (2) Multiple Oral Dose Studies

Abstract

In this study, the dosage regimen for rantidine in patients with renal dysfunction, which was previouly proposed, has been evaluated in patients with renal impairment.
1. Twenty patients with renal impairment with the creatinine clearance (Clcr) of less than 70 ml/min were chosen. The oral dose of ranitidine 50 mg b. i. d. was repeatedly given to five non-dialyzed patients with severe renal impairment with the Clcr of less than 30 ml/min for 14 days, and also ranitidine, 100 mg b. i. d., to five non-dialyzed patients with moderate renal impairment with the Clcr of 30 to 70 ml/min for the same period. The oral dose of ranitidine of 50 mg b. i. d. was repeatedly given for 4 to 5 weeks to ten hemodialyzed patients with renal failure.
2. In the non-dialyzed patients, actual measurement values of plasma ranitidine concentrations after 7 and 14 days of medication were almost in keeping with simulation curve of plasma concentrations at the repeatedly administered period, which were calculated from the results obtained when initially administered. In addition, it was assumed that the maximum steady state plasma concentrations (Css, max) were 409.3±122. 5 ng/ml (patients with severe renal impairment), and 558.0±62.4ng/ml (patients with moderate renal impairment), and the minimum concentrations in steady state (Css, max) were 101.9±26.0ng/ml (patients with severe renal impairment) and 103.3±254ng/ml (patients with moderate renal impairment).
3. Ranitidine was effectively removed from blood by hemodialysis, and Css, max and Css, min in the hemodialyzed patients were considered approximately 320ng/ml and 180ng/ml, respectively.
As stated above, an excess rise of plasma ranitidine concentrations in both non-dialyzed and dialyzed patients was not observed and the sufficient concentrations for proper clinical effects were obtained. Thus, the appropriate ranitidine regimen was proposed for each: 50 mg b. i. d. for the patients with Clcr less than 30 ml/min and 100 mg b. i. d. for the patients with Clcr of 30 to 70 ml/min.