VETERINARY DRUGS - DISPOSITION, BIOTRANSFORMATION AND RISK-EVALUATION

Veterinary drugs may only be produced, distributed and administered af ter being licensed. This implies that, prior to marketing, a critical evalution of the pharmaceutical quality, the clinical efficacy and the over-all pharmacological and toxicological properties of the active s ubstances will be performed by national and/or supranational authoriti es. However, despite a sophisticated legal (harmonized) framework, a n umber of factors involved in residue formation and safety assessment r emain unpredictable or dependant on the current 'state of the art' in the understanding of molecular pharmacology and toxicology. For exampl e, drug disposition and residue formation in the target animal species may be influenced by a broad variety of physiological parameters incl uding age, sex and diet, as well as by pathological conditions especia lly the acute phase response to infection. These factors affect both d rug disposition and metabolite formation. Furthermore, current thinkin g in toxicological risk assessment is influenced by recent development s in molecular toxicology and thus by an increased but still incomplet e understanding of the interaction of a toxic compound with the living organism. General recognized principles in the evaluation of potentia l toxicants are applied in the recommendation of withdrawal times and the establishment of maximum residue limits (MRL values). Apart from t oxicological-based assessment, increasing awareness is directed to oth er than toxicological responses, especially the potential risk of effe cts of antimicrobial residues on human gastrointestinal microflora. Th us, the methodology of risk assessment is discussed in the context of the recently established legal framework within the European Union.