Serum pharmacokinetics of oxytetracycline in sheep and calves and tissue residues in sheep following a single intramuscular injection of a long-acting preparation

The pharmacokinetics of a long-acting oxytetracycline (OTC) formulation (Liquamycin(R) LA-200(R)) injected intramuscularly (i.m.) at a dose of 20 mg/kg were determined in four calves and 24 sheep to determine if the approved label dose for cattle provided a similar serum time/concentration profile in sheep. The AUC for the calves was 168 +/- 14.6 (mug. h/mL) and was significantly less than the AUC for sheep (209 +/- 43 mug. h/mL). Using the standard two-stage approach and a one-compartment model, the mean C-max for the calves was 5.2 +/- 0.8 mug/mL, and for the sheep was 6.1 +/- 1.3 mug/mL. The mean terminal phase rate constants were 0.031 and 0.033 h, and the V-dss were 3.3 and 3.08 L/kg for the calves and sheep respectively. Analysis of the data using the standard two-stage approach, the naive pooled-data approach and a population model gave very similar results for both the cattle and sheep data. Sheep tissue residues of OTC in serum, liver, kidney, fat, muscle and injection site were measured at 1, 2, 3, 5, 7 and 14 days after a single i.m, injection of 20 mg/kg OTC. Half-lives of OTC residues in the tissues were 38.6, 33.4, 28.6, 25.4, 21.3, and 19.9 h for injection site, kidney, muscle, liver, mesenteric fat and renal fat, respectively. The ratio of tissue to serum concentration was fairly consistent at all slaughter times, except for the fat and injection sites. The mean ratios were 1.72, 4.19, 0.11, 0.061, 0.84 and 827 for the liver, kidney, renal fat, mesenteric fat, muscle and injection sites, respectively. The tissue concentrations of OTC residues were below the established cattle tolerances for OTC in liver (6 p.p.m.), muscle (2 p.p.m.) and kidney (12 p.p.m.) by 48 h, and in injection site muscle by 14 days after the single i.m. injection of 20 mg/kg.