Pharmacokinetics of oxytetracycline and therapeutic implications in veal calves

Abstract

Pharmacokinetic parameters of oxytetracycline were analysed in healthy preruminant veal calves after intravenous, intramuscular and oral administration. The serum half-lives in the beta-elimination phase of both 10% and 20% solutions after i.v. injection of 10 mg/kg were similar (7.07 +/- 1.36 h and 7.16 +/- 1.17 h, mean +/- SD), whereas the total body clearance and the apparent volume of distribution were higher for the 20% solution. Serum concentrations above 0.5 microgram/ml were maintained with both formulations during 12-24 h but were only above 4 micrograms/ml to 5 h. Intramuscular administration of the 20% solution gave a complete absorption with two rate constants of absorption, a faster (t1/2 alpha 1 = 0.27 h) and a slower one (t1/2 alpha 2 = 10.90 h) responsible for the delayed elimination half-life after this route of application (t1/2 beta = 9.83 +/- 1.35 h). Mean serum concentrations reached a maximum level of 3.01 +/- 0.72 micrograms/ml at 4.01 +/- 2.84 h and decreased to 0.5 microgram/ml between 12 and 24 h. 50 mg/kg given orally with a milk replacer were found to have a mean bioavailability of 46.35%. A mean serum peak level of 4.99 +/- 1.37 micrograms/ml was achieved at 9.16 +/- 1.99 h and the mean concentration was still above 0.5 microgram/ml after 48 h. The elimination half-life (t1/2 beta = 10.66 +/- 3.15 h) reflected the slow absorption step (t1/2 alpha 2 = 10.15 h) following that responsible for the initial faster absorption (t1/2 alpha 1 = 1.99 h). Comparison of the area under the serum curves gave mean values of 117% for tetracycline and of 53% for chlortetracycline relative to oxytetracycline (arbitrarily fixed at 100%) after identical oral dosage of the three tetracyclines. We also propose and discuss a dosage schedule based on minimal inhibitory concentrations of different susceptible pathogens.