The effect of renal function on the pharmacokinetics of ranitidine.

This open study evaluated the influence of renal function on the pharmacokinetics of ranitidine (50 mg i.v. infusion given over 6 min). Five groups, each of 8 subjects, 1 with normal renal function and 4 with different degrees of renal impairment were studied. Renal function was assessed in each patient by 51Cr-EDTA (glomerular filtration rate, GFR), creatinine clearance (GFR) and N-methylnicotinamide clearance (reflecting glomerular and tubular function). Sixteen blood samples (5 ml) taken up to 48 h post dose from each subject were analysed for plasma ranitidine concentrations by reversed phase HPLC. Patient groups with renal impairment had significantly increased AUC infinity and t1/2 with corresponding decreases in CLp and lambda z when compared with normal subjects. There was also a significant increase in tmax but not in Cmax. There was a high linear correlation between the degree of renal impairment and ranitidine clearance. In patients with GFR < or = 20 ml min-1, the AUC infinity mean ratio (compared with normal subjects) was up to 4.6 while for patients with GFR 20-50 ml min-1, the average AUC infinity ratio was 2.6. It is recommended that the dose of ranitidine is halved in patients with GFR < or = 20 ml min-1.