Desloratadine (DCL) undergoes metabolism to form 3-OH-DCL by an unidentified enzyme(s). Approximately 7% of the general population and 20% of blacks are thought to be DSMs, i.e. they form little to no 3-OH-DCL and have higher DCL concentrations due to a longer DCL half-life.

Open-label, single oral 5 mg dose administered to healthy adult males and females aged 18–55 years. Blood samples were collected pre-dose and at 1, 2, 3, 4, 6, 7, 8, 12, and 24 hours to measure plasma DCL and 3-OH-DCL concentrations by LC/MS/MS. Exposure measures were computed by non compartmental methods using WinNonlin. C_max and T_max were determined from observed data and DSMs identified by AUC_{(3-OH DCL)}:AUC_(DCL) ratios <0.1.

14/170 subjects (8.2%) were identified as DSMs. Mean ± SD AUC_(0–24) for normal metabolizers (NMs) and DSMs was 27114 ± 2425 pg·hr/mL and 41955 ± 2263 pg·hr/mL, respectively. Median T_max was 3 hours (range 1–7) in NMs and 12 hours (range 6–24) in DSMs. Mean ± SD C_24h for NMs and DSMs was 507 ± 250 pg/mL and 1782 ± 623 pg/mL.

Plasma concentrations rise and fall more slowly in DSMs. DSMs are exposed to higher concentrations of DCL with a 3.5-fold increase in DCL concentration at the end of the dosing interval (C_24h) following a single dose. With repetitive daily dosing systemic exposure to DCL in DSMs will be many times greater than in NMs. Consequently, DSMs will accumulate DCL and be more susceptible to concentration-related adverse effects. Older patients with co-morbidities and concomitant medications may be most at risk.