The optical resolution of racemic chlorpheniramine and its stereoselective pharmacokinetics in rat plasma.

Abstract

An ovomucoid-conjugated column has been developed for the chiral stationary-phase liquid chromatographic resolution of racemic chlorpheniramine with a quantitation limit of 0.05 microgram mL-1. The assay was used to study the stereoselective kinetics of chlorpheniramine enantiomers in rats. After bolus intravenous administration of racemic chlorpheniramine maleate (20 mg kg-1), plasma concentration of the (-)-form was higher than that of the (+)-form. In the elimination phase, the concentrations of (+)- and (-)-chlorpheniramine in the plasma declined biexponentially with half-lives of 18.2 and 50.0 min, respectively. Although there was no significant difference in blood-to-plasma concentration ratio of both enantiomers, the apparent total blood clearance of (+)-chlorpheniramine was twice as large as that of the (-)-isomer. Binding of (-)-chlorpheniramine to rat plasma protein was stronger than that of (+)-chlorpheniramine suggesting stereoselective pharmacokinetics may be due to a difference in the plasma protein binding.