Clarinex - Clinical Pharmacology

Desloratadine

• Clarinex - Drug Description
• Clarinex - Side Effects & Drug Interactions
• Clarinex - Warnings & Precautions
• Clarinex - Additional Info
• Clarinex - Overdosage & Contraindications
• Clarinex - Indications & Dosage
• Clarinex - Patient Info

CLINICAL PHARMACOLOGY

Mechanism of Action

Desloratadine is a long-acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity. Receptor binding data indicates that at a concentration of 2-3 ng/ mL (7 nanomolar), desloratadine shows significant interaction with the human hista-mine H1-receptor.

Desloratadine inhibited histamine release from human mast cells in vitro. Results of a radiolabeled tissue distribution study in rats and a radioligand H1-receptor binding study in guinea pigs showed that desloratadine did not readily cross the blood brain barrier.

Pharmacokinetics

Absorption:

Following oral administration of desloratadine 5 mg 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 area under the concentration-time curve (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 CLARINEX RediTabs Tablets was evaluated in a three-way crossover study in 30 adult volunteers. A single CLARINEX RediTabs Tablet containing 5 mg of desloratadine was bioequivalent to a single 5 mg CLARINEX Tablet and was bioequivalent to 10 mL of CLARINEX Syrup containing 5 mg of deslor-atadine for both desloratadine and 3-hydroxydesloratadine.

In a separate study with 30 adult volunteers, food or water had no effect on the bioavailability (AUC and Cmax) of CLARINEX RediTabs Tablets, however, food shifted the desloratadine median Tmax value from 2.5 to 4 hr. 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-hydroxydeslor-atadine, an active metabolite, which is subsequently glucuronidated. The enzyme( s) responsible for the formation of 3-hydroxydesloratadine have not been identified.