A wide range of veterinary medicines is used to treat animals in the UK. Whilst the environmental impact of selected substances (particulary the sheep dip chemicals, anthelmintics and fish farm chemicals) has been well studied, limited information is available in the public domain on the other groups of substances (e.g. antifungals, coccidiostats, antiprotozoals, hormones and growth promoters). There is therefore a need to identify other substances that may impact the environment in order to design national monitoring programmes, target experimental work and develop pollution prevention methodologies. In this study, a simple two-stage prioritisation scheme was developed and applied to veterinary medicines in use in the UK. In the first stage, those substances that have high potential to enter the environment in significant amounts were identified on the basis of amounts used in the UK, treatment type and metabolism. In stage 2, the hazard of the identified substances to terrestrial and aquatic organisms was assessed. Using the approach, a total of 56 substances or groups were assigned to a 'high priority' category. For eleven of these substances, sufficient data were available to characterise their risk, these were: oxytetracycline, chlortetracycline, tetracycline, sulphadiazine, amoxicillin, diazinon, tylosin, dihydrostreptomycin, apramycin, cypermethrin and sarafloxicin. For the remaining 45 substances, full datasets were not available and it is recommended that in the first instance, attempts are made to fill these data gaps.

The complexity of multiple species approvals continues throughout the life of a product as post-approval manufacturing changes, as well as all generic versions of approved products, are evaluated for each of the approved target animal species. In comparing product bioavailability across animal species, it is not unusual to observe marked interspecies differences. For many compounds, these differences reflect species-specific presystemic metabolism. However, a host of other variables must also be considered, including in vivo drug solubility, gastric transit time, intestinal permeability, diet, and species-by-formulation interactions. To predict potential species-by-formulation interactions, one must consider the solubility and intestinal permeability of the drug entity, the type of formulation, nature of the excipients, and the physiological characteristics of the animal recipient. In this paper, we examine manufacturing and formulation variables that can affect drug bioavailability, and the potential for species-specific differences in the responses to these formulations.

Proper veterinary care of horses requires that horses in training have access to modern therapeutic medication. However, the sensitivity of equine drug testing now allows for detection of pharmacologically insignificant concentrations of many therapeutic medications. In 1995, the Association of Racing Commissioners International (ARCI) resolved that members 'address trace level detection so as not to lead to disciplinary action based on pharmacologically insignificant traces of these substances'. The rationale behind this approach is to prevent overly-sensitive testing from inhibiting the proper and appropriate veterinary care of performance horses. This review describes a scientific approach to implement this resolution using local anaesthetics as a model system and compares this approach with others currently in place. For the purpose of this discussion, a 'trace' concentration is defined as a pharmacologically-insignificant concentration. Initially, the target pharmacological effect (e.g. local anaesthesia) was identified, and the dose response relationship was quantified. The 'Highest No Effect Dose'(HNED) was estimated and then administered to horses. Next, the target analyte was identified, synthesized, if necessary, and quantified in blood or urine; the concentrations observed after administration of the HNED are, by definition, true concentrations and hence are pharmacologically insignificant. The key to this approach has been the synthesis of a unique series of authentic equine metabolite standards, which has allowed scientific identification of the concentration at which the pharmacological effect was indistinguishable from control values. Traces found at less than this concentration are, by definition,'no effect limits','no effect traces'(NETs),'no effect cut-offs','no effect limitations on the sensitivity of testing', or 'subtherapeutic residues'. Conversely, this approach will also identify potent medications for which the sensitivity of testing may need to be improved. Within the context of these experiments, the data create an analytical/pharmacological database that should assist industry professionals in interpreting the significance of trace concentrations of these medications or their metabolites in official samples. The most favourable outcome of this research is more medically appropriate use of therapeutic medications in performance horses, yielding substantial benefits to the health and welfare of these horses.

The aim of our study was to evaluate antimicrobial use in dogs and cats in Finland. Information on veterinary prescriptions was gathered from University Pharmacies (n=17) over a one-month period, April 2001. A total of 2719 prescriptions for veterinary use were delivered, of which the majority were for dogs (70%, n=1898) and cats (14%, n=384). The most prescribed therapy group was per-oral antimicrobial agents (53%, n=1449), of which 16%(n=237) were medicines approved for humans. The most commonly used substances for dogs and cats were betalactams, 66% and 78%, respectively. The proportion of fluoroquinolones was 3-5%. The average duration of the treatment periods was 10 days with the exception of treatment of cats with macrolide-lincosamides, where the mean period was 20 days. Indication was mentioned only in 37% of the prescriptions.

To point out which antibiotics and NSAIDs are safe to use during pregnancy of the dog and which are not, a simple system for classification has been developed for veterinarians. To find out more information about what drugs and during what stage of pregnancy veterinarians prescribe, a random survey was carried out among veterinarians who work primarily with companion animals. To develop this system for classification, literature concerning the teratogenicity of veterinary drugs was evaluated. The results of the survey indicate that the possibility of a pregnancy is rarely taken into account when prescribing medications and that many drugs that have not been proven safe, are prescribed. From the evaluation of literature follows that benzylpenicillin, amoxicillin with or without clavulanic acid, cefadroxil, cefalexin and lincomycin are the safest and therefore the agents of choice during pregnancy. It would be better if NSAIDs were not to be used during the last stage of pregnancy, because they might cause delay of the delivery. Drugs that might be teratogenic should be avoided unless there is no alternative and the possible benefits for the bitch outweigh the risks for the foetus.

The primary reason for developing the ARCI Uniform Classification of Foreign Substances was to give stewards and other racing regulators guidelines to assist them in understanding the relative performance effects and general offensiveness to the Rules of Racing of various drugs and medications. As such, these guidelines have been very useful in the world of racing regulation--officially or unofficially--because this classification system, for the first time, places a relative number on the inappropriateness of any one of more than 750 agents appearing in forensic samples taken from racing horses. The guidelines set up by this system established the first framework for dialogue among veterinary pharmacologists reviewing these drugs. Prior to development of the guidelines, pharmacologists had their own opinions about these agents and their effects on performance. The guidelines, however, established a framework for discussion, and there has been surprising unanimity about the classification of each of these agents. Not only does this classification system provide a useful basis for dialogue among experts, it is also useful for regulators, horsemen and other laymen, most of whom have little training or experience with drugs and their effects on horses. The system is easily understandable and communicates the relative possibility of any classified substance to affect the performance of a horse. Consequently, the system has made it possible for laymen to understand the degree of impropriety of all drugs and medicines with which they may have contact. Grouping a large number of drugs into specific classes has greatly facilitated discussion about regulations and penalties, and the classification system is related to proposed penalty guidelines which were developed in parallel. With regard to penalties for Class 1 agents, it is easy to assign and defend substantial penalties after examining the guideline statement describing the possible performance effects of this group of agents as well as the fact that they have no well recognized therapeutic role. Similarly, the relatively modest effects of class 4 and 5 agents, combined with the fact that these groups encompass a large number of well recognized therapeutic agents, helps in understanding the possible presence of trace levels of these agents in post-race samples. In summary, the ARCI Uniform Classification of Foreign Substances Guidelines condenses data on drugs and medications and places them into a simple five class system. This system has made it possible to confidently discuss the regulatory implications of the identification of any one of the approximately 750 classified substances potentially found in forensic samples from a performance horse. As such it facilitates both the development and implementation of more understandable and equitable regulatory processes.