title: Pharmacokinetics and pharmacodynamics of d-chlorpheniramine following intravenous and oral administration in healthy Thoroughbred horses.
abstract: The pharmacokinetics of d-chlorpheniramine (CPM), a histamine H1-receptor antagonist, and its ability to inhibit of histamine-induced cutaneous wheal formation, were studied in healthy Thoroughbred horses (n=5). Following an intravenous (IV) dose of 0.5mg/kg bodyweight (BW), plasma drug disposition was very rapid, with the mean terminal half-life and total body clearance calculated as 2.7h and 0.7 L/h/kg, respectively. The observed maximal inhibition of wheal formation following IV doses of 0.1 and 0.5mg/kg BW were 37.8% and 60.6% at 0.5h, respectively. Oral administration of CPM (0.5mg/kg BW) resulted in a bioavailability of 38%, which induced a peak plasma drug concentration at 1h and a maximal inhibition of wheal formation (39%) at 2h. A pharmacokinetic/pharmacodynamic link model showed that CPM in horses has lower efficacy, much lower potency and slightly lower sensitivity than other reported antihistamines. These results indicated that CPM should be administered at frequent intervals or at large dose rates to maintain therapeutic concentrations in horses.
authors.affiliation: Miho Training Centre Equine Clinic, Japan Racing Association (JRA), 2500-2, Mikoma, Miho-mura, Inashiki, Ibaragi 300-0493, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kuroda
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Nagata
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takizawa
authors.forename: Norihisa
authors.initials: N
authors.lastname: Tamura
authors.forename: Kanichi
authors.initials: K
authors.lastname: Kusano
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mizobe
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hariu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002744:Chlorpheniramine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006736:Horses / Q000097:blood* / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male
chemical_list: D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine
keywords: Antihistamine; Horse; Pharmacodynamics; Pharmacokinetics; d-Chlorpheniramine