A Pharmacokinetic Profile of Desloratadine in Healthy Adults, Including Elderly

Abstract

Objective: To characterise the pharmacokinetic profile of desloratadine and its main metabolite, 3-hydroxy (3-OH) desloratadine, in a patient population representative of the population studied in the desloratadine clinical efficacy and safety studies, including the elderly.

Design: A multicentre, multidose, open-label pharmacokinetic trial.

Participants: 113 healthy adult volunteers (57 men, 56 women; 95 White, 18 Black) were enrolled, and 112 completed the study.

Interventions: A 5mg oral dose of desloratadine once daily for 10 days.

Main outcome measures: C_max, t_max, t1/2 and AUC_24h.

Results: Steady-state plasma concentrations were attained by day 7. Peak plasma concentrations (C_max) of desloratadine (mean 3.98 μg/L) and 3-OH desloratadine (mean 1.99 μg/L) were reached at a mean of 3.17 and 4.76 hours (t_max), respectively, after administration. The area under the plasma concentration-time curve from 0 to 24 hours (AUC_24h) was 56.9 μg/L · h for desloratadine and 32.3 μg/L · h for 3-OH desloratadine. The mean half-lives (t1/2) of desloratadine and 3-OH desloratadine were 26.8 and 36 hours, respectively. There were no clinically relevant differences in the calculated pharmacokinetic parameters of desloratadine when participants were stratified into 3 age groups (19 to 45, 46 to 64 and 65 to 70 years). Treatment-emergent adverse events occurred in 31 of the 113 participants (3 of the 17 aged ≥65 years reported adverse events). All adverse events were mild to moderate in severity, and none resulted in discontinuation of treatment. There were no consistent clinically relevant changes in blood pressure, pulse, oral body temperature or electrocardiogram evaluations and no reports of syncope or sedation.

Conclusion: Daily administration of desloratadine 5mg is well tolerated. The 27-hour half-life of desloratadine permits once daily administration. No dosage adjustment of desloratadine is required in the elderly.