LANSOPRAZOLE PHARMACOKINETICS IN SUBJECTS WITH VARIOUS DEGREES OF KIDNEY-FUNCTION

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 samp les were obtained after doses 1 and 7 of the once-daily seven-dose reg imen, and plasma concentrations of lansoprazole and five metabolites w ere quantitated with use of HPLC. The free fraction of lansoprazole in creased as kidney function declined. A significant, although weak, rel ationship existed between creatinine clearance (CLCR) and area under t he plasma concentration versus time awe (AUG) and terminal disposition half-life (t(1/2)), calculated with total concentration data. Those i ndividuals with lower CLCR values also had lower total AUC and t(1/2) values. However, there was no statistically significant relationship b etween CLCR and peak plasma concentration or AUC calculated with unbou nd concentration data. No adjustment of lansoprazole dose is recommend ed on the basis of impaired kidney function.