Pharmacokinetics of lansoprazole in patients with renal or liver disease of varying severity

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 t_1/2 of L were doubled, without any change in C_max. In cirrhotics t_max was prolonged, the AUC was increased (P<0.001) and there was prolongation of t_1/2 (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 (C_max, R_m) and a decrease in the hydroxylated metabolite (C_max, R_m) 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.