Desloratadine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Desloratadine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Desloratadine is a long acting tricyclic histamine antagonist with selective H 1 -receptor histamine antagonist activity. Receptor binding data indicate that at a concentration of 2 to 3 ng/mL (7 nanomolar), desloratadine shows significant interaction with the human histamine H 1 receptor. Desloratadine inhibited histamine release from human mast cells in vitro . Results of a radiolabeled tissue distribution study in rats and a radioligand H 1 -receptor-binding study in guinea pigs showed that desloratadine does not readily cross the blood brain barrier. The clinical significance of this finding is unknown. Pseudoephedrine sulfate is an orally active sympathomimetic amine and exerts a decongestant action on the nasal mucosa. Pseudoephedrine sulfate is recognized as an effective agent for the relief of nasal congestion due to allergic rhinitis. Pseudoephedrine produces peripheral effects similar to those of ephedrine and central effects similar to, but less inte
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Desloratadine is a long acting tricyclic histamine antagonist with selective H 1 -receptor histamine antagonist activity.
Receptor binding data indicate that at a concentration of 2 to 3 ng/mL (7 nanomolar), desloratadine shows significant interaction with the human histamine H 1 receptor.
Desloratadine inhibited histamine release from human mast cells in vitro .
Results of a radiolabeled tissue distribution study in rats and a radioligand H 1 -receptor-binding study in guinea pigs showed that desloratadine does not readily cross the blood brain barrier.
The clinical significance of this finding is unknown.
Pseudoephedrine sulfate is an orally active sympathomimetic amine and exerts a decongestant action on the nasal mucosa.
Pseudoephedrine sulfate is recognized as an effective agent for the relief of nasal congestion due to allergic rhinitis.
Pseudoephedrine produces peripheral effects similar to those of ephedrine and central effects similar to, but less intense than, amphetamines.
It has the potential for excitatory side effects.
12.2 Pharmacodynamics Wheal and Flare: Human histamine skin wheal studies following single and repeated 5 mg doses of desloratadine have shown that the drug exhibits an antihistaminic effect by 1 hour; this activity may persist for as long as 24 hours.
There was no evidence of histamine-induced skin wheal tachyphylaxis within the desloratadine 5 mg group over the 28-day treatment period.
The clinical relevance of histamine wheal skin testing is unknown.
Effects on QT c : In clinical trials for CLARINEX-D 12 HOUR Extended Release Tablets, ECGs were recorded at baseline and endpoint within 1 to 3 hours after the last dose.
The majority of ECGs were normal at both baseline and endpoint.
No clinically meaningful changes were observed following treatment with CLARINEX-D 12 HOUR Extended Release Tablets for any ECG parameter, including the QT c interval.
An increase in the ventricular rate of 7.1 and 6.4 bpm was observed in the CLARINEX-D 12 HOUR Extended Release Tablets and pseudoephedrine groups, respectively, compared to an increase of 3.2 bpm in subjects receiving desloratadine alone.
Single daily doses of CLARINEX 45 mg were given to normal male and female volunteers for 10 days.
All ECGs obtained in this study were manually read in a blinded fashion by a cardiologist.
In the CLARINEX-treated subjects, there was a mean increase in the maximum heart rate of 9.2 bpm relative to placebo.
The QT interval was corrected for heart rate (QT c ) by both Bazett's and Fridericia methods.
Pharmacokinetics
12.3 Pharmacokinetics Absorption: In a single dose pharmacokinetic study, the mean time to maximum plasma concentrations (T max ) for desloratadine occurred at approximately 4 to 5 hours post dose and mean peak plasma concentrations (C max ) and area under the concentration-time curve (AUC) of approximately 1.09 ng/mL and 31.6 ng∙hr/mL, respectively, were observed. In another pharmacokinetic study, food and grapefruit juice had no effect on the bioavailability (C max and AUC) of desloratadine. For pseudoephedrine, the mean T max occurred at 6 to 7 hours post dose and mean peak plasma concentrations (C max ) and area under the concentration-time curve (AUC) of approximately 263 ng/mL and 4588 ng∙hr/mL, respectively, were observed. Food had no effect on the bioavailability (C max and AUC) of pseudoephedrine. Following oral administration of CLARINEX-D 12 HOUR Extended Release Tablets twice daily for 14 days in healthy volunteers, steady-state conditions were reached on Day 10 for desloratadine, 3-hydroxydesloratadine and pseudoephedrine. For desloratadine, mean steady-state peak plasma concentrations (C max ) and area under the concentration-time curve AUC 0-12 hrs of approximately 1.7 ng/mL and 16 ng∙hr/mL were observed, respectively. For pseudoephedrine, mean steady-state peak plasma concentrations (C max ) and AUC 0-12 hrs of 459 ng/mL and 4658 ng∙hr/mL were observed. Distribution: Desloratadine and 3-hydroxydesloratadine are approximately 82% to 87% and 85% to 89%, bound to