title: Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration.
abstract: The pharmacokinetics of indomethacin (1 mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3-3.0 microg/mL) from 5 to 50 min after i.v. and from 5 to 60-90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (+/- SD) volumes of distribution at steady state (Vd(ss)) were 4.10 +/- 1.40 and 4.21 +/- 1.93 L/kg and the mean clearance values (ClB) were 0.17 +/- 0.06 and 0.22 +/- 0.12 L/h x kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection (t1/2beta = 17.4 +/- 4.6 and 21.25 +/- 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration (Cmax = 1.10 +/- 0.68 microg/mL) was reached 10 min after dosing; the absorption phase was fast (Kab = 26 +/- 18 h(-1)) and short (t1/2ab = 2.33 +/- 1.51 min) and the mean bioavailability was 91.0 +/- 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.
authors.affiliation: Cátedra de Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Vinagre
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez
authors.forename: M I
authors.initials: MI
authors.lastname: San Andrés
authors.forename: J C
authors.initials: JC
authors.lastname: Boggio
authors.forename: M D
authors.initials: MD
authors.lastname: San Andrés
authors.forename: T
authors.initials: T
authors.lastname: Encinas
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D005260:Female; D006207:Half-Life; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D012756:Sheep / Q000097:blood*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin