Chlorpheniramine plasma concentration and histamine H1-receptor occupancy.

S U Yasuda, A Wellstein, P Likhari, J T Barbey, R L Woosley

Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.

Clinical pharmacology and therapeutics 1995 Aug

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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.

Citation

S U Yasuda, A Wellstein, P Likhari, J T Barbey, R L Woosley. Chlorpheniramine plasma concentration and histamine H1-receptor occupancy. Clinical pharmacology and therapeutics. 1995 Aug;58(2):210-20