title: Pharmacokinetics of intravenously, intramuscularly and intra-adiposely administered carazolol in pigs.
abstract: The beta-blocking agent carazolol is used for the prevention of stress syndromes in pigs. Little is known of the pharmacokinetics of this drug, and therefore of its residue status in meat. In this study carazolol pharmacokinetics were investigated in a randomized three-way cross-over design in five pigs. A dose of 0.025 mg/kg was given intravenously, intramuscularly and intra-adiposely (in the subcutaneous fat layer). Carazolol was rapidly distributed and had a short half-life of 1.2-4.2 h. The distribution volume was calculated to be 0.22-0.65 l/kg. After intramuscular or intra-adipose administration the absorption pattern was biphasic. A rapid initial phase was followed by a slow second phase. Absorption was found to be incomplete at 24 h after intramuscular and intra-adipose administration ranging from 24 to 59% and 25 to 66%, respectively. The biphasic behaviour could be explained by retention of the drug in the tissues after absorption of the solvent was complete. A few hours after intravenous administration only negligible amounts of the drug were circulating in the body; however, considerable amounts of drug might have remained at the intramuscular or intra-adipose injection site.
authors.affiliation: Department of Pharmaceutics, University of Utrecht, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Kadir
authors.forename: J
authors.initials: J
authors.lastname: Zuidema
authors.forename: A
authors.initials: A
authors.lastname: Pijpers
authors.forename: R
authors.initials: R
authors.lastname: Melendez
authors.forename: A
authors.initials: A
authors.lastname: Vulto
authors.forename: J H
authors.initials: JH
authors.lastname: Verheijden
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011897:Random Allocation; D013552:Swine / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C014382:carazolol