PHARMACOKINETICS OF ORALLY-ADMINISTERED LEVOCABASTINE IN PATIENTS WITH RENAL-INSUFFICIENCY

The effects of renal insufficiency and hemodialysis on the pharmacokin etics of orally administered levocabastine were studied in six nondial ysis patients and in six patients undergoing regular hemodialysis. Lev ocabastine .5 mg, supplied as a solution, was administered orally to e ach patient 1 hour after breakfast. Compared with data in healthy volu nteers, the oral absorption and disposition of levocabastine were impa ired in patients with renal insufficiency. The time to reach peak plas ma concentration was increased and the peak plasma concentration was d ecreased in the patients with renal insufficiency compared with health y volunteers. Urinary excretion of the unchanged drug, which is the ma jor elimination pathway of levocabastine, was reduced in the patients with renal insufficiency. The decreased urinary excretion most likely contributed to the prolonged half-life (from 36 hours to 95 hours) and increased area under the plasma concentration-time curve (+56%) in th e patients with renal insufficiency as compared with the healthy volun teers. Although the a-hour hemodialysis procedure starting 4 hours aft er dosing eliminated 10% of the oral dose, the terminal half-life and the total area under the plasma concentration-time curve did not diffe r significantly between the hemodialysis and the nonhemodialysis patie nts. In conclusion, the current study showed that the initial oral abs orption of levocabastine is reduced and that levocabastine elimination is prolonged in patients with renal insufficiency.