Disposition of desloratadine in healthy volunteers

Abstract

Background Desloratadine (DL), a major active metabolite of loratadine (LOR), is a long-acting tricyclic antihistamine with selective peripheral histamine H1-receptor antagonist activity. The objective of this study was to characterize the absorption, metabolism and excretion of DL following oral capsule administration. Methods Six healthy male volunteers (ages 18–40 years) received a single 10mg (100μCi) 14C-DL dose in a Phase 1, open-label study. Blood, urine and feces were collected over 240 hr. Results DL was well absorbed. With the exception of a single subject, DL was extensively metabolized; major pathway consisted of hydroxylation and subsequent glucuronidation. 3OH-DL-glucuronide was identified as a primary plasma metabolite (47% of circulating plasma 14C). Drug-derived radioactivity was excreted in both urine (41%) and feces (47%). One subject, identified as a poor metabolizer, exhibited 10-fold greater exposure to DL and correspondingly lower amounts of 3OH-DL in plasma and excreta. Disposition of DL in this subject was characterized by slow absorption, slow metabolism and prolonged elimination (t½=110 hr vs. mean t½=19.5 hr, n=5). All metabolites detected following DL administration were characterized following an oral LOR dose. Conclusions Characterization of metabolite and excretion profile of orally administered DL identified a phenotypic polymorphism of DL metabolism. Further clinical studies confirmed lack of safety concern associated with this phenomenon. Clinical Pharmacology & Therapeutics (2005) 77, P48–P48; doi: 10.1016/j.clpt.2004.12.074