Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration |
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Authors: | B Vinagre C RodrÍguez M I San AndrÉs J C Boggio M D San AndrÉs & T Encinas |
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Institution: | Cátedra de Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, Spain and;*Cátedra de Farmacología, Facultad de Agronomía y Veterinaria, Universidad Nacional del Litoral, Argentina |
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Abstract: | The pharmacokinetics of indomethacin (1mg/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 μg/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 ( V dss) were 4.10 ± 1.40 and 4.21 ± 1.93 L/kg and the mean clearance values ( C lB) were 0.17 ± 0.06 and 0.22 ± 0.12 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 ½β = 17.4 ± 4.6 and 21.25 ± 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration ( C max = 1.10 ± 0.68 μg/mL) was reached 10 min after dosing; the absorption phase was fast ( K ab = 26 ± 18 h-1) and short ( t ½ab = 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. |
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