Pharmacokinetics of ranitidine in patients with chronic renal failure.
The pharmacokinetic behaviour of a single oral 150 mg ranitidine dose was studied in six patients with severe chronic renal failure (CRF) (creatinine clearance 2-18 ml/min) and compared to that in ten patients with duodenal ulceration but normal renal function (N) (creatinine clearance 69-125 ml/min). Although the maximum concentrations (Cmax) were significantly higher in CRF group when compared to N group (p less than 0.025) there was no difference in the time taken to reach Cmax (tmax). The area under the curve (AUC) was also significantly larger in the CRF group (p less than 0.001) than in the N group. Within the CRF group there was a large variation in Cmax (CV = 38%) and AUC (46%) which may reflect variable bioavailability of ranitidine. The terminal elimination rate constant (beta) was significantly smaller (p less than 0.001) in CRF group when compared with N group resulting in a median t1/2 for the CRF group of 7.3 h, 2.4 times that of N group. The recovery of unchanged ranitidine in the urine was significantly less in CRF group (p less than 0.001) despite a great interindividual variation in both groups. A significant linear relationship between beta and creatinine clearance was shown (r = 0.81 p less than 0.001). The results indicate that ranitidine elimination is appreciably reduced in renal failure. It is tentatively suggested that the standard 150 mg dose should be halved while keeping the dose interval unchanged at twelve hours in patients with severe renal failure (creatinine clearance less than 30 ml/min).
D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011899:Ranitidine / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D011899:Ranitidine