Rebound following hemodialysis of cimetidine and its metabolites.

Abstract

The effect of hemodialysis on the pharmacokinetics of cimetidine and its metabolites was studied after the intravenous administration of a 300-mg dose of cimetidine. Serum concentrations were monitored before, during, and after hemodialysis. Cimetidine pharmacokinetics were similar to those in patients with end-stage renal failure, with a total body clearance of 3.3 +/- 1.0 mL/min/kg and a half-life of 4.1 hours. Dialysis caused an initial decrease in serum concentrations for cimetidine, hydroxymethyl cimetidine, and cimetidine sulfoxide, followed by a rebound in serum concentrations immediately after treatment. Dialysis clearances, as calculated from extraction ratios, were 83 +/- 15, 90 +/- 16, 93 +/- 24, and 126 +/- 23 mL/min for cimetidine, hydroxymethyl, sulfoxide, and creatinine, respectively. After four hours of dialysis, 10% +/- 3.2% of the cimetidine dose was recovered in the dialysate. The sulfoxide and hydroxymethyl metabolites demonstrated relatively constant serum concentrations for up to 24 hours postdosing, and therefore, estimates of their terminal half-lives were not possible. In one patient, accumulation of both metabolites occurred during multiple dosing. Hemodialysis is an ineffective means of decreasing the total body load of cimetidine and its metabolites. Presumably, sequestration of the drug in body tissues decreases the amount of drug present in the blood available for dialysis removal, with rebound occurring due to postdialysis re-equilibriation between blood and extravascular fluids.