Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Summary The pharmacokinetics of lansoprazole (L) after a single oral dose of 30 mg was determined in 18 healthy volunteers, 17 renal failure patients and 24 hepatic failure patients; 8 hepatitis and 16 with compensated (CC) or uncompensated (UCC) cirrhosis. In renal failure, the absorption of L was unchanged, its half-life being similar to that in healthy subjects; a small change seen in mild renal failure patients (creatinine clearance between 40 and 60 ml/min) was attributed to the age of the patients. Urinary elimination, essentially as metabolites of lansoprazole, was decreased, in relation to the degree of renal impairment. In hepatitis patients, the AUC and t1/2 of L were doubled, without any change in Cmax. In cirrhotics tmax was prolonged, the AUC was increased (P〈0.001) and there was prolongation of t1/2 (6.1 h in CC and 7.2 h in UCC compared to 1.4 h in healthy subjects). These changes resulted from a decrease in the clearance of L. There was also an increase in its sulphone metabolite (Cmax, Rm) and a decrease in the hydroxylated metabolite (Cmax, Rm) in relation to the degree of liver disease, and reflecting a decrease in hydroxylation and biliary elimination. Thus, renal failure had no effect on the pharmacokinetics of L, but severe hepatic failure caused marked changes. A repeated dosing study would be necessary to evaluate the repercussions of the possible accumulation in cirrhotic patients.
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