Allegra D - Clinical Pharmacology

CLINICAL PHARMACOLOGY

Mechanism of Action

Fexofenadine hydrochloride, the major active metabolite of terfenadine, is an antihistamine with selective peripheral H1-receptor antagonist activity. Fexofenadine hydrochloride inhibited antigen-induced bronchospasm in sensitized guinea pigs and histamine release from peritoneal mast cells in rats.

In laboratory animals, no anticholinergic or alpha1-adrenergic-receptor blocking effects were observed. Moreover, no sedative or other central nervous system effects were observed. Radiolabeled tissue distribution studies in rats indicated that fexofenadine does not cross the blood-brain barrier.

Pseudoephedrine hydrochloride is an orally active sympathomimetic amine and exerts a decongestant action on the nasal mucosa. Pseudoephedrine hydrochloride 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. At the recommended oral dose, it has little or no pressor effect in normotensive adults.

Pharmacokinetics

The pharmacokinetics of fexofenadine hydrochloride and pseudoephedrine hydrochloride when administered separately have been well characterized. Fexofenadine pharmacokinetics were linear for oral doses of fexofenadine hydrochloride up to 120 mg twice daily. The mean elimination half-life of fexofenadine was 14.4 hours following administration of 60 mg fexofenadine hydrochloride, twice daily, to steady-state in normal volunteers. Human mass balance studies documented a recovery of approximately 80% and 11% of the [14C] fexofenadine hydrochloride dose in the feces and urine, respectively. Approximately 5% of the total dose was metabolized.

Because the absolute bioavailability of fexofenadine hydrochloride has not been established, it is unknown if the fecal component is unabsorbed drug or the result of biliary excretion. The pharmacokinetics of fexofenadine hydrochloride in seasonal allergic rhinitis patients were similar to those in healthy subjects. Peak fexofenadine plasma concentrations were similar between adolescent (12-16 years of age) and adult patients. Fexofenadine is 60% to 70% bound to plasma proteins, primarily albumin and 1-acid glycoprotein.