title: Chlorpheniramine plasma concentration and histamine H1-receptor occupancy.
abstract: 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.
authors.affiliation: Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: S U
authors.initials: SU
authors.lastname: Yasuda
authors.forename: A
authors.initials: A
authors.lastname: Wellstein
authors.forename: P
authors.initials: P
authors.lastname: Likhari
authors.forename: J T
authors.initials: JT
authors.lastname: Barbey
authors.forename: R L
authors.initials: RL
authors.lastname: Woosley
mesh_terms: D000328:Adult; D000818:Animals; D002744:Chlorpheniramine / Q000097:blood* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases; D010641:Phenotype; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D012016:Reference Values
chemical_list: D011969:Receptors, Histamine H1; D002744:Chlorpheniramine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6