FACTORS AFFECTING THE WITHDRAWAL PERIOD OF AMOXICILLIN FROM VETERINARY MEDICINAL PRODUCTS USED IN FOOD-PRODUCING ANIMALS

Abstract

The withdrawal period of active substance residues from the animal’s body which products are intended for human consumption is an important criterion for the safety of veterinary medicinal products. This products cannot be authorized without establishing this important parameter. There are a number of veterinary medicinal products on the market of Ukraine and EU member states, which have the same active substance in the same concentration and pharmaceutical formulation, but the withdrawal period can differ significantly. The goal of our study was to determine the influence of various factors on the withdrawal period of amoxicillin from single-component oral (powders) and injectable (suspensions, long acting suspensions) dosage forms, which are included in the State Register of Veterinary Medicines of Ukraine and EU product database (UPD). As is known, amoxicillin is widely used for the treatment of infectious diseases in humans and animals, in particular food-producing ones, which are a source of food products intended for human consumption. From the point of the hazard of development acquired antimicrobial resistance when consuming products of animal origin contaminated with residues, the duration of the established withdrawal period is a question of great importance. As shown in the study results, the pharmacokinetic parameters of veterinary medicinal products, in particular bioavailability, as well as clinical characteristics of the disease, have a significant impact on the duration of the withdrawal period. Usually, the withdrawal period depends on the type of dosage form, and the amount and nature of excipients, because oral and injectable pharmaceutical formulations of the same veterinary medicinal product differ in terms of bioavailability from the systemic circulation and the site of injection. It was also defined that the duration of the withdrawal period depends on the amount of the administered dose of the veterinary medicinal product, the treatment duration, the target animal species, fasting conditions (before or after feeding), and the substrates used for feeding (dissolving in water or mixing with feed), analytical methods used to determine active substances or their metabolites, methods of the statistical processing results and differences between individual values established in a group of animals involved in the study. The importance of approving the withdrawal period for generic veterinary medicinal products manufactured by different companies is confirmed by studies carried out by the European Medicines Agency order at the request of the Competent authorities of individual EU countries in connection with the detection of the overestimated residue level compared with the established maximum limits over time, defined as the withdrawal period specified during product authorization. In two cases, changes were made to the Summary of Product Characteristics and package leaflets, regarding the extension of the withdrawal period of amoxicillin from certain tissues and for different target animal species. Marketing authorization holders are recommended to harmonize the withdrawal period for generic products with the established value for the reference veterinary medicinal products.