Disposition of loratadine in healthy volunteers

Abstract

The absorption, metabolism and excretion of carbon-14-labeled loratadine (LOR, SCH 29851, Claritin®) administered orally to healthy male volunteers were evaluated. Following a single oral 10-mg dose of [¹⁴C]LOR (∼102 µCi), concentrations of LOR and desloratadine (DL; a pharmacologically active descarboethoxy metabolite of LOR) were determined in plasma. Metabolites in plasma, urine and feces were characterized using a liquid chromatography-mass spectrometry system (LC-MS) connected in line with a flow scintillation analyzer (FSA). Maximum plasma LOR and DL concentrations were achieved at 1.5 h and 1.6 h, respectively; thus, LOR was rapidly absorbed but also rapidly metabolized as indicated by these similar t_max values. Metabolite profiles of plasma showed that LOR was extensively metabolized via descarboethoxylation, oxidation and glucuronidation. Major circulating metabolites included 3-hydroxy-desloratadine glucuonide (3-OH-DL-Glu), dihydroxy-DL-glucuronides, and several metabolites resulting from descarboethoxylation and oxidation of the piperidine ring. LOR was completely metabolized by 6 h post-dose. LOR-derived radiocarbon was excreted almost equally in the urine (41%) and feces (43%). About 13% of the dose was eliminated in the urine as 3-OH-DL-Glu. DL accounted for less than 2% of the dose recovered in the urine and only trace amounts of LOR were detected. 3-OH-DL was the major fecal metabolite (∼17% of the dose). The combined amount of 5- and 6-hydroxy-DL contributed to an additional 10.7% of the dose in feces. Approximately 5.4% and 2.7% of the dose were excreted in the feces as unchanged drug and DL, respectively.

Key Words::

• Loratadine
• desloratadine
• metabolism
• radioactivity
• LC-MS
• human

Acknowledgements

The authors thankfully acknowledge all LOR-related synthetic efforts of the Radiochemistry Group at SPRI under the direction of Dr Paul McNamara. We are also grateful to Dr James Hubbell (SPRI) for fruitful discussions. Finally, the authors thank PPD Pharmaco, Inc. for quantitative bioanalysis support.