PHARMACOKINETICS OF INDOMETHACIN IN SHEEP AFTER INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATION

The pharmacokinetics of indomethacin (1 mg/kg) was determined in six a dult sheep after intravenous (i.v.) and intramuscular (i.m.) injection . Plasma concentrations were maintained within the therapeutic range ( 0.3-3.0 mu g/mL) from 5 to 50 min after i.v. and from 5 to 60-90 min a fter i.m. administration. After two trials, indomethacin best fitted a n 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 an d the mean clearance values (Cl-B) were 0.17 +/- 0.06 and 0.22 +/- 0.1 2 L/h.kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection (t(1/2 beta) = 17.4 +/- 4.6 and 21.25 +/- 4.44 h, i.v. and i .m. respectively). After i.m. administration, plasma maximum concentra tion (C-max = 1.10 +/- 0.68 mu g/mL) was reached 10 min after dosing; the absorption phase was fast (K-ab = 26 +/- 18 h(-1)) and short (t(1/ 2ab) = 2.33 +/- 1.51 min) and the mean bioavailability was 91.0 +/- 32 .8%, although there was considerable interanimal variation. In some in dividuals, bioavailability was higher than 100%. This fact combined wi th the slower elimination phase after i.m. than after i.v. administrat ion, could be related with enterohepatic recycling.