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.
Glaxo Research and Development Ltd., Stockley Park West, Uxbridge, Middlesex, UK.
J S
JS
Dixon
J M
JM
Borg-Costanzi
S J
SJ
Langley
L F
LF
Lacey
S
S
Toon
D000328:Adult; D000704:Analysis of Variance; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000502:physiology*; D007674:Kidney Diseases / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D011899:Ranitidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012016:Reference Values
D011899:Ranitidine