Absorption 

Following oral administration of a desloratadine 5 mg tablet once daily for 10 days to normal healthy volunteers, the mean time to maximum plasma concentrations (Tmax) occurred at approximately 3 hours post dose and mean steady state peak plasma concentrations (Cmax) and AUC of 4 ng/mL and 56.9 ng∙hr/mL were observed, respectively. Neither food nor grapefruit juice had an effect on the bioavailability (Cmax and AUC) of desloratadine. 

The pharmacokinetic profile of desloratadine oral solution was evaluated in a three-way crossover study in 30 adult volunteers. A single dose of 10 mL of desloratadine oral solution containing 5 mg of desloratadine was bioequivalent to a single dose of 5 mg desloratadine tablet. Food had no effect on the bioavailability (AUC and Cmax) of desloratadine oral solution. 

Distribution 

Desloratadine and 3-hydroxydesloratadine are approximately 82% to 87% and 85% to 89% bound to plasma proteins, respectively. Protein binding of desloratadine and 3-hydroxydesloratadine was unaltered in subjects with impaired renal function. 

Metabolism 

Desloratadine (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of 3-hydroxydesloratadine have not been identified. Data from clinical trials indicate that a subset of the general population has a decreased ability to form 3-hydroxydesloratadine, and are poor metabolizers of desloratadine. In pharmacokinetic studies (n=3748), approximately 6% of subjects were poor metabolizers of desloratadine (defined as a subject with an AUC ratio of 3-hydroxydesloratadine to desloratadine less than 0.1, or a subject with a desloratadine half-life exceeding 50 hours). These pharmacokinetic studies included subjects between the ages of 2 and 70 years, including 977 subjects aged 2 to 5 years, 1575 subjects aged 6 to 11 years, and 1196 subjects aged 12 to 70 years. There was no difference in the prevalence of poor metabolizers across age groups. The frequency of poor metabolizers was higher in Blacks (17%, n=988) as compared to Caucasians (2%, n=1,462) and Hispanics (2%, n=1,063). The median exposure (AUC) to desloratadine in the poor metabolizers was approximately 6-fold greater than in the subjects who are not poor metabolizers. Subjects who are poor metabolizers of desloratadine cannot be prospectively identified and will be exposed to higher levels of desloratadine following dosing with the recommended dose of desloratadine. In multidose clinical safety studies, where metabolizer status was identified, a total of 94 poor metabolizers and 123 normal metabolizers were enrolled and treated with desloratadine oral solution for 15 to 35 days. In these studies, no overall differences in safety were observed between poor metabolizers and normal metabolizers. Although not seen in these studies, an increased risk of exposure-related adverse events in patients who are poor metabolizers cannot be ruled out. 

Elimination 

The mean plasma elimination half-life of desloratadine was approximately 27 hours. Cmax and AUC values increased in a dose proportional manner following single oral doses between 5 and 20 mg. The degree of accumulation after 14 days of dosing was consistent with the half-life and dosing frequency. A human mass balance study documented a recovery of approximately 87% of the 14C-desloratadine dose, which was equally distributed in urine and feces as metabolic products. Analysis of plasma 3-hydroxydesloratadine showed similar Tmax and half-life values compared to desloratadine. 

Special Populations 

Geriatric Subjects:

In older subjects (≥65 years old; n=17) following multiple-dose administration of desloratadine tablets, the mean Cmax and AUC values for desloratadine were 20% greater than in younger subjects (<65 years old). The oral total body clearance (CL/F) when normalized for body weight was similar between the two age groups. The mean plasma elimination half-life of desloratadine was 33.7 hr in subjects ≥65 years old. The pharmacokinetics for 3-hydroxydesloratadine appeared unchanged in older versus younger subjects. These age-related differences are unlikely to be clinically relevant and no dosage adjustment is recommended in elderly subjects.

Pediatric Subjects:

In subjects 6 to 11 years old, a single dose of 5 mL of desloratadine oral solution containing 2.5 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg desloratadine tablet. In subjects 2 to 5 years old, a single dose of 2.5 mL of desloratadine oral solution containing 1.25 mg of desloratadine, resulted in desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg desloratadine tablet. However, the Cmax and AUC of the metabolite (3-hydroxydesloratadine) were 1.27 and 1.61 times higher for the 5 mg dose of oral solution administered in adults compared to the Cmax and AUC obtained in children 2 to 11 years of age receiving 1.25 to 2.5 mg of desloratadine oral solution. 

A single dose of either 2.5 mL or 1.25 mL of desloratadine oral solution containing 1.25 mg or 0.625 mg, respectively, of desloratadine was administered to subjects 6 to 11 months of age and 12 to 23 months of age. The results of a population pharmacokinetic analysis indicated that a dose of 1 mg for subjects aged 6 to 11 months and 1.25 mg for subjects 12 to 23 months of age is required to obtain desloratadine plasma concentrations similar to those achieved in adults administered a single 5 mg dose of desloratadine oral solution. 

Renally Impaired:

Desloratadine pharmacokinetics following a single dose of 7.5 mg were characterized in patients with mild (n=7; creatinine clearance 51 to 69 mL/min/1.73 m2), moderate (n=6; creatinine clearance 34 to 43 mL/min/1.73 m2), and severe (n=6; creatinine clearance 5 to 29 mL/min/1.73 m2) renal impairment or hemodialysis dependent (n=6) patients. In patients with mild and moderate renal impairment, median Cmax and AUC values increased by approximately 1.2- and 1.9-fold, respectively, relative to subjects with normal renal function. In patients with severe renal impairment or who were hemodialysis dependent, Cmax and AUC values increased by approximately 1.7- and 2.5-fold, respectively. Minimal changes in 3-hydroxydesloratadine concentrations were observed. Desloratadine and 3-hydroxydesloratadine were poorly removed by hemodialysis. Plasma protein binding of desloratadine and 3-hydroxydesloratadine was unaltered by renal impairment. Dosage adjustment for patients with renal impairment is recommended [see DOSAGE AND ADMINISTRATION (2.5)]. 

Hepatically Impaired:

Desloratadine pharmacokinetics were characterized following a single oral dose in patients with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment as defined by the Child-Pugh classification of hepatic function and 8 subjects with normal hepatic function. Patients with hepatic impairment, regardless of severity, had approximately a 2.4-fold increase in AUC as compared with normal subjects. The apparent oral clearance of desloratadine in patients with mild, moderate, and severe hepatic impairment was 37%, 36%, and 28% of that in normal subjects, respectively. An increase in the mean elimination half-life of desloratadine in patients with hepatic impairment was observed. For 3-hydroxydesloratadine, the mean Cmax and AUC values for patients with hepatic impairment were not statistically significantly different from subjects with normal hepatic function. Dosage adjustment for patients with hepatic impairment is recommended [see DOSAGE AND ADMINISTRATION (2.5)]. 

Gender:

Female subjects treated for 14 days with desloratadine tablets had 10% and 3% higher desloratadine Cmax and AUC values, respectively, compared with male subjects. The 3-hydroxydesloratadine Cmax and AUC values were also increased by 45% and 48%, respectively, in females compared with males. However, these apparent differences are not likely to be clinically relevant and therefore no dosage adjustment is recommended. 

Race:

Following 14 days of treatment with desloratadine tablets, the Cmax and AUC values for desloratadine were 18% and 32% higher, respectively, in Blacks compared with Caucasians. For 3-hydroxydesloratadine there was a corresponding 10% reduction in Cmax and AUC values in Blacks compared to Caucasians. These differences are not likely to be clinically relevant and therefore no dose adjustment is recommended. 

Drug Interactions:

In two controlled crossover clinical pharmacology studies in healthy male (n=12 in each study) and female (n=12 in each study) volunteers, desloratadine 7.5 mg (1.5 times the daily dose) once daily was coadministered with erythromycin 500 mg every 8 hours or ketoconazole 200 mg every 12 hours for 10 days. In three separate controlled, parallel group clinical pharmacology studies, desloratadine at the clinical dose of 5 mg has been coadministered with azithromycin 500 mg followed by 250 mg once daily for 4 days (n=18) or with fluoxetine 20 mg once daily for 7 days after a 23-day pretreatment period with fluoxetine (n=18) or with cimetidine 600 mg every 12 hours for 14 days (n=18) under steady-state conditions to normal healthy male and female volunteers. Although increased plasma concentrations (Cmax and AUC 0 to 24 hrs) of desloratadine and 3-hydroxydesloratadine were observed (see Table 2), there were no clinically relevant changes in the safety profile of desloratadine, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs, and adverse events.