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Chlorpheniramine plasma concentration and histamine H 1 ‐receptor occupancy
Author(s) -
Yasuda Sally Usdin,
Wellstein Anton,
Likhari Paul,
Barbey Jean T.,
Woosley Raymond L.
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90199-x
Subject(s) - dextromethorphan , pharmacology , antihistamine , antagonist , chemistry , histamine , active metabolite , chlorpheniramine maleate , metabolite , receptor antagonist , histamine h1 receptor , cyp2d6 , receptor , medicine , pharmacokinetics , chromatography , metabolism , biochemistry , cytochrome p450
The plasma concentration‐response relationship of the antihistamine chlorpheniramine is poorly characterized. This study examined concurrently the concentrations of chlorpheniramine and presence of H 1 ‐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 H 1 ‐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 H 1 ‐receptor antagonist in plasma. In addition, a role is suggested for CYP2D6 in formation of a potent active metabolite of chlorpheniramine. Clinical Pharmacology & Therapeutics (1995) 58 , 210–220; doi: