The Optical Resolution of Racemic Chlorpheniramine and Its Stereoselective Pharmacokinetics in Rat Plasma

Abstract

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 μg 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.