Effect of race and sex on single and multiple dose pharmacokinetics of desloratadine

Objective: This study was designed to characterise the single and multiple dose pharmacokinetic profile of desloratadine, a new antihistamine, and its main metabolite, 3-hydroxy (3-OH) desloratadine, in healthy volunteers differing in sex and race. Design: An open-label, parallel-group, single- and multiple-dose pharmacokinetic trial. Intervention: A single 7.5mg oral tablet of desloratadine on day 1, followed by 7.5mg daily doses on days 4 to 17. Participants: 48 healthy, nonsmoking volunteers (12 White men, 12 Black men, 12 White women, 12 Black women). Main outcome measures: AUC(24h) and C-max determined from serial blood samples of desloratadine and 3-OH desloratadine. Results: There were no clinically relevant differences between men and women or Black participants and White participants for desloratadine and 3-OH desloratadine maximum plasma concentrations (C-max) and area under the plasma concentration-time curve (AUC). Following multiple doses, the geometric mean C-max was 5.17 mug/L in men, 5.68 mug/L in women, 5.87 mug/L in Black participants and 5.00 mug/L in White participants; the corresponding AUC from 0 to 24 hours (AUC(24h)) values were 77.9, 80.0, 90.6 and 68.8 mug/L . h. Corresponding 3-OH desloratadine geometric mean Cmax values were 1.93, 2.79, 2.20 and 2.45 mug/L, and the AUC24h values were 32.1, 47.5, 37.1 and 41.1 mug/L . h. Conclusions: Oral administration of multiple doses of desloratadine 7.5mg, a dose 50% higher than the recommended 5mg clinical dose, was well tolerated by healthy adults differing in sex and race. Comparison of the C-max and AUC values following 14 days of treatment with desloratadine indicates that no dosage adjustment is needed on the basis of sex or race.