PHARMACOKINETICS OF LANSOPRAZOLE IN PATIENTS WITH RENAL OR LIVER-DISEASE OF VARYING SEVERITY

The pharmacokinetics of lansoprazole (L) after a single oral dose of 3 0 mg was determined in 18 healthy volunteers, 17 renal failure patient s and 24 hepatic failure patients; 8 hepatitis and 16 with compensated (CC) or uncompensated (UCC) cirrhosis. In renal failure, the absorpti on of L was unchanged, its half-life being similar to that in healthy subjects; a small change seen in mild renal failure patients (creatini ne clearance between 40 and 60 ml/min) was attributed to the age of th e patients. Urinary elimination, essentially as metabolites of lansopr azole, was decreased, in relation to the degree of renal impairment. I n hepatitis patients, the AUC and t1/2 of L were doubled, without any change in C(max). In cirrhotics t(max) was prolonged, the AUC was incr eased (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 res ulted from a decrease in the clearance of L. There was also an increas e in its sulphone metabolite (C(max), R(m)) and a decrease in the hydr oxylated metabolite (C(max), R(m)) in relation to the degree of liver disease, and reflecting a decrease in hydroxylation and biliary elimin ation. Thus, renal failure had no effect on the pharmacokinetics of L, but severe hepatic failure caused marked changes. A repeated dosing s tudy would be necessary to evaluate the repercussions of the possible accumulation in cirrhotic patients.