¹Departments of Pharmacokinetics and Biopharmaceutics, Biotransformation, and Clinical Pharmacology, Abbott Laboratories, Abbott Park, Ill.

Correspondence: Michael D. Karol, PhD, Pharmacokinetics and Biopharmaceutics, D4PK AP13A-3, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500.

^*Funded in part by a grant-in-aid from TAP Pharmaceuticals, Deerfield, Ill.

Received 1 December 1994; Accepted 28 October 1996.

Abstract

The pharmacokinetics of lansoprazole, a new benzimidazole proton pump inhibitor, was evaluated after multiple-dose oral administration to 20 subjects with various degrees of kidney function. Multiple blood samples were obtained after doses 1 and 7 of the once-daily seven-dose regimen, and plasma concentrations of lansoprazole and five metabolites were quantitated with use of HPLC. The free fraction of lansoprazole increased as kidney function declined. A significant, although weak, relationship existed between creatinine clearance (CL_CR) and area under the plasma concentration versus time curve (AUC) and terminal disposition half-life (t_½), calculated with total concentration data. Those individuals with lower CL_CR values also had lower total AUC and t_½ values. However, there was no statistically significant relationship between CL_CR and peak plasma concentration or AUC, calculated with unbound concentration data. No adjustment of lansoprazole dose is recommended on the basis of impaired kidney function.