Clemastin Pharmacology, Pharmacokinetics, Studies, Metabolism - Clemastine

Clemastin Pharmacology, Pharmacokinetics, Studies, Metabolism - Clemastine

CLINICAL PHARMACOLOGY

Clemastine fumarate is an antihistamine with anticholinergic (drying) and sedative side effects. Antihistamines competitively antagonize various physiological effects of histamine including increased capillary permeability and dilatation, the formation of edema, the “flare” and “itch” response, and gastrointestinal and respiratory smooth muscle constriction. Within the vascular tree, H₁- receptor antagonists inhibit both the vasoconstrictor and vasodilator effects of histamine. Depending on the dose, H₁- receptor antagonists can produce CNS stimulation or depression. Most antihistamines exhibit central and/or peripheral anticholinergic activity. Antihistamines act by competitively blocking H₁- receptor sites. Antihistamines do not pharmacologically antagonize or chemically inactivate histamine, nor do they prevent the release of histamine.

Pharmacokinetics

Antihistamines are well-absorbed following oral administration. Chlorpheniramine maleate, clemastine fumarate, and diphenhydramine hydrochloride achieve peak blood levels within 2-5 hours following oral administration. The absorption of antihistamines is often partially delayed by the use of controlled release dosage forms. In these instances, plasma concentrations from identical doses of the immediate and controlled release dosage forms will not be similar. Tissue distribution of the antihistamines in humans has not been established.

Antihistamines appear to be metabolized in the liver chiefly via mono- and didemethylation and glucuronide conjugation. Antihistamine metabolites and small amounts of unchanged drug are excreted in the urine. Small amounts of the drugs may also be excreted in breast milk.

In normal human subjects who received histamine injections over a 24-hour period, the antihistaminic activity of clemastine reached a peak at 5-7 hours, persisted for 10-12 hours and in some cases, for long as 24 hours. Pharmacokinetic studies in man utilizing ³H and ¹⁴C labeled compound demonstrates that: clemastine is rapidly absorbed from the gastrointestinal tract, peak plasma concentrations are attained in 2-4 hours, and urinary excretion is the major mode of elimination.