Clemastine

Clemastine is an H₁-receptor antagonist. It belongs to the benzhydryl ether group of antihistamines. Clemastine inhibits selectively the histamine receptors of the H₁ type and reduces capillary permeability. It exerts a potent antihistaminic and antipruritic effect with a fast onset and long duration of action up to 12 hours.

Absorption

Following oral administration clemastine is almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are attained within 2-4 hours. The antihistaminic activity of the drug reaches its peak after 5 to 7 hours; it usually persists for 10 to 12 hours, in some cases, however, for up to 24 hours.

Distribution

Plasma protein binding of clemastine amounts to 95%.

Biotransformation

Clemastine undergoes extensive metabolism in the liver.

Elimination

Elimination from plasma occurs biphasically, with half-lives of 3.6 ± 0.9 hours and 37 ± 16 hours. The major route of metabolite excretion (45 to 65%) is through the kidneys into urine, where only trace amounts of the parent compound are found. In lactating women, small amounts of the drug may pass into breast milk.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction at therapeutically relevant doses.

In a rat study, a reduction in pup survival, at doses more than 200X the therapeutic dose, was observed when mothers were treated through lactation.