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.

Sodium meclofenamate is a non-steroidal anti-inflammatory drug with anaphylactic protective activity in cattle. The objectives of this study were to describe the pharmacokinetic behaviour of sodium meclofenamate after intravenous and oral administration to sheep and to determine the influence of closure of the reticular groove on the bioavailability of the drug. Sodium meclofenamate was administered by the intravenous (2.2 mg/kg) and oral (20 mg/kg) routes to sheep (n = 6). During the oral study the reticular groove was closed by intravenous administration of lysine vasopressin (0.3 IU/kg) or left open (saline solution). The closure of the reticular groove was assessed by determination of the blood glucose curves after oral administration of a glucose solution. After intravenous administration of meclofenamate, the distribution and elimination half-lives of the drug were 7.2 min and 542 min respectively, Vss was 1.68 L/kg and ClB was 2.47 mliter/min kg. Two different patterns of the plasma concentration curves were observed after oral administration of sodium meclofenamate. When the reticular groove was closed, two peaks were observed (tmax-1 12-15 min, Cmax-1 3.30-24.01 micrograms/mliter; and tmax-2' 52.50-75 min, Cmax-2, 6.45-11.08 micrograms/mliter).

The pharmacokinetics of indomethacin (7 mg/kg) was determined in six adult sheep after intraruminal administration. The plasma concentration–time curves showed different patterns for each sheep, depending on the physiological state of the gastrointestinal tract, where absorption took place, and possible enterohepatic and saliva recycling. Indomethacin was irregularly and poorly absorbed from the rumen after intraruminal administration to sheep. Plasma concentrations barely rose to the lower therapeutic margin and mean bioavailability was 38.25 ± 15.98 %. The elimination phase was slow (β = 0.015 ± 0.010 h–1) and the half‐life was long (t1/2β = 56.52 ± 31.21 h). The mean residence time was 20.01 ± 6.92 h.

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