Chlorpheniramine plasma concentration and histamine H1-receptor occupancy.
The plasma concentration-response relationship of the antihistamine chlorpheniramine is poorly characterized. This study examined concurrently the concentrations of chlorpheniramine and presence of H1-receptor antagonist in plasma after administration of 8 mg chlorpheniramine in normal volunteers. Six extensive metabolizers and five poor metabolizers, as judged by CYP2D6 phenotype (dextromethorphan metabolic ratio), ... were enrolled in the study. More than 80% occupancy of H1-receptors by antagonist in plasma was observed for 12 hours after the dose in extensive metabolizers and greater than 60% from 12 to 30 hours in poor metabolizers, when plasma concentrations had fallen below those that should result in 50% occupancy of receptors. The results suggest that (+/-)-chlorpheniramine plasma concentrations do not predict H1-receptor antagonist in plasma. In addition, a role is suggested for CYP2D6 in formation of a potent active metabolite of chlorpheniramine.
Mesh Terms:
Adult, Animals, Chlorpheniramine, Chromatography, High Pressure Liquid, Cytochrome P-450 CYP2D6, Cytochrome P-450 Enzyme System, Dose-Response Relationship, Drug, Female, Guinea Pigs, Humans, Male, Mixed Function Oxygenases, Phenotype, Receptors, Histamine H1, Reference Values
Adult, Animals, Chlorpheniramine, Chromatography, High Pressure Liquid, Cytochrome P-450 CYP2D6, Cytochrome P-450 Enzyme System, Dose-Response Relationship, Drug, Female, Guinea Pigs, Humans, Male, Mixed Function Oxygenases, Phenotype, Receptors, Histamine H1, Reference Values
Clin. Pharmacol. Ther.
Date: Aug. 01, 1995
PubMed ID: 7648771
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