Disposition of desloratadine in healthy volunteers

Abstract

The absorption, metabolism and excretion of desloratadine (DL, Clarinex®) were characterized in six healthy male volunteers. Subjects received a single oral 10-mg dose of [¹⁴C]DL (∼104 µCi). Blood, urine and feces were collected over 240 h. DL was well absorbed; drug-derived radioactivity was excreted in both urine (41%) and feces (47%). With the exception of a single subject, DL was extensively metabolized; the major biotransformation pathway consisted of hydroxylation at the 3 position of the pyridine ring and subsequent glucuronidation (3-OH-DL-glucuronide or M13). In five of the six subjects, DL was slowly eliminated (mean t_½ = 19.5 h) and persisted in the plasma for 48–120 h post-dose. This is in contrast to a t_½ of ∼110 h and quantifiable plasma DL concentrations for the entire 240-h sampling period in one subject, who was identified phenotypically as a poor metabolizer of DL. This subject also exhibited correspondingly lower amounts of M13 in urine and 3-OH-DL (M40) in feces. Disposition of DL in this subject was characterized by slow absorption, slow metabolism and prolonged elimination. Further clinical studies confirmed the lack of safety issues associated with polymorphism of DL metabolism (Prenner et al. 2006, Expert Opinion on Drug Safety, 5: 211–223).

Key Words::

• Desloratadine
• human metabolism
• LC-MS
• loratadine
• polymorphism
• poor metabolizer

Acknowledgements

The authors 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.