PHYSIOLOGICAL DISTRIBUTION AND METABOLIC INACTIVATION OF CHLORCYCLIZINE AND CYCLIZINE

¹ The Wellcome Research Laboratories, Burroughs Wellcome & Co. (U.S.A.) Inc., Tuckahoe, New York

The metabolic inactivation, tissue distribution and protein binding of chiorcycizine· HCl (Perazil) and cycizine · HCl (Marezine) have been studied in dogs and rats.

The major route of cycizine and chlorcydizine metabolism in vivo and in vitro is through their corresponding demethylated derivatives, norcyclizine and norchlorcyclizine, which have little if any antihistaminic activity.

A sex difference in the metabolism of chlorcyclizine by the rat has been found with the male rat forming norchlorcyclizine at a much faster rate than the female.

Chiorcyclizine, cyclizine and their demethylated derivatives are distributed in all the tissues of the rat, with the highest levels being found in the lung, kidney, spleen and liver.

The dog converts chlorcyclizine to norchlorcyclizine more slowly than the rat; however, chronic treatment of the dog with chlorcyclizine leads to an increased conversion to norchlorcycizine.

Chlorcyclizine and norchlorcycizine are metabolized slower than are cycizine and norcyclizine. This finding may be explained by the more avid binding of the former compounds to plasma protein.