The optical resolution of racemic chlorpheniramine and its stereoselective pharmacokinetics in rat plasma.
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.
Department of Pharmaceutics I, Tohoku College of Pharmacy, Sendai, Japan.
E
E
Sakurai
S
S
Yamasaki
Y
Y
Iizuka
N
N
Hikichi
H
H
Niwa
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002744:Chlorpheniramine / Q000097:blood* / Q000302:isolation & purification / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D001798:Blood Proteins; D002744:Chlorpheniramine