Age-dependent pharmacokinetics of oxytetracycline in ruminants.

Abstract

Oxytetracycline (OTC) was administered intravenously (i.v.) to 3- and 12-week-old calves and lactating cows, and both i.v. and intramuscularly (i.m.) to 14-week-old calves and non-lactating cows. Concentrations of OTC were determined in plasma and were analysed kinetically. The pharmacokinetic parameters which were derived using the three-compartment open model were inadequate to describe plasma drug levels in six out of the 23 animals treated i.v., and, therefore, model-independent kinetic parameters were utilized for evaluating age-dependent pharmacokinetics of OTC. In the 3-week-old calves, the total body clearance (ClB) was 0.0022 ml/min/kg, the total distribution volume (Vd area) was 2.48 l/kg, and the distribution volume of the central compartment (V1) was 0.56 l/kg. Mean values for ClB, Vd area, and V1 in 3-week-old calves were two-, three- and four-fold greater, respectively, than the corresponding values in cows. Mean values of ClB and Vd area for the 12- and 14-week-old calves were intermediate between the corresponding values in 3-week-old calves and cows. Dose and state of lactation did not affect the model-independent parameters. The i.v. and i.m. data illustrated that the recommended dose levels of OTC in young calves should be twice those employed in cows for obtaining similar plasma OTC concentration--time profiles.