Effect of milking interval and lactation stage on withdrawal period: exemplified with a bovine oxytetracycline lactation physiologically based kinetic model

To safeguard human health, it is critical to avoid potentially harmful residues of veterinary drugs in dairy products. The aim of this study was to evaluate the impact of milk production on the excretion of drugs into milk using physiologically based kinetic (PBK) modeling with oxytetracycline as a case study. A nonlinear model for milk volume was developed to accurately describe the volume of milk within a cow's udder. The model was evaluated through Monte Carlo simulations and subsequently integrated into an established whole-body oxytetracycline PBK model for cows. The enhanced model facilitated simulations to ascertain the influence of lactation stage and milking interval on drug withdrawal periods. The findings indicated that for oxytetracycline, a drug characterized by low milk excretion, both the stage of lactation and the frequency of milking had minimal impact on the withdrawal period. However, simulations revealed that milking cows once a day, as opposed to twice, could extend the withdrawal period for one day. The timing of drug administration was found to have no impact on the withdrawal period for this particular drug. The model's reliance on a-priori estimated parameters ensured that the predictions of the distribution and elimination of compounds within the udder compartment were solely dependent on lactation stage and milking intervals. This feature also allowed for the simulation of studies without milk volume data. Nevertheless, to formulate generalized recommendations on withdrawal periods, compounds with varying physicochemical properties must be evaluated.