[The reclassification assistant: Drug reclassification made easy]. / Umwidmungs-Assistent: Arzneimittelumwidmung leicht gemacht.

INTRODUCTION: In Switzerland, just over 700 veterinary medicinal products are authorized. Nevertheless, in practice veterinarians are often confronted with extraordinary situations in which a suitable veterinary medicinal product is not authorized, unavailable or otherwise not applicable. For livestock and horses in particular, this poses a challenge for pharmacotherapy due to food safety regulations. In these cases, the reclassification assistant can be used to determine whether and how a medicinal product containing the appropriate drug can be reclassified and correctly applied in food-producing animals. The users will be guided step by step with selectable options through the online assistant. If the desired reclassification is permitted in the legal framework, information on the withdrawal periods to be observed for the chosen medicinal product will be provided. This online assistant follows an algorithm based on the reclassification cascade and applicable food safety regulations.

INTRODUCTION: En Suisse, un peu plus de 700 médicaments vétérinaires sont autorisés. Néanmoins, dans la pratique, les vétérinaires sont souvent confrontés à des situations extraordinaires dans lesquelles un médicament vétérinaire approprié n'est ni autorisé, ni disponible, ni utilisable pour d'autres raisons. En particulier pour le bétail et les chevaux, cela pose un défi pour la pharmacothérapie en raison de la réglementation sur la sécurité alimentaire. Dans ces cas, l'assistant de reconversion peut être utilisé pour déterminer si et comment un médicament contenant le principe actif approprié peut être reconverti et correctement appliqué. Les utilisateurs seront guidés pas à pas avec des options sélectionnables via l'assistant en ligne. Si la reconversion souhaitée est autorisée dans le cadre légal, des informations sur les délais d'attente à respecter pour le médicament choisi seront fournies. Cet assistant en ligne suit un algorithme basé sur la cascade de reconversion les réglementations applicables en matière de sécurité alimentaire.

Multi-class multi-residue analysis of veterinary drugs in meat using enhanced matrix removal lipid cleanup and liquid chromatography-tandem mass spectrometry.

This study presents the development and validation of a quantitation method for the analysis of multi-class, multi-residue veterinary drugs using lipid removal cleanup cartridges, enhanced matrix removal lipid (EMR-Lipid), for different meat matrices by liquid chromatography tandem mass spectrometry detection. Meat samples were extracted using a two-step solid-liquid extraction followed by pass-through sample cleanup. The method was optimized based on the buffer and solvent composition, solvent additive additions, and EMR-Lipid cartridge cleanup. The developed method was then validated in five meat matrices, porcine muscle, bovine muscle, bovine liver, bovine kidney and chicken liver to evaluate the method performance characteristics, such as absolute recoveries and precision at three spiking levels, calibration curve linearity, limit of quantitation (LOQ) and matrix effect. The results showed that >90% of veterinary drug analytes achieved satisfactory recovery results of 60-120%. Over 97% analytes achieved excellent reproducibility results (relative standard deviation (RSD) < 20%), and the LOQs were 1-5 µg/kg in the evaluated meat matrices. The matrix co-extractive removal efficiency by weight provided by EMR-lipid cartridge cleanup was 42-58% in samples. The post column infusion study showed that the matrix ion suppression was reduced for samples with the EMR-Lipid cartridge cleanup. The reduced matrix ion suppression effect was also confirmed with <15% frequency of compounds with significant quantitative ion suppression (>30%) for all tested veterinary drugs in all of meat matrices. The results showed that the two-step solid-liquid extraction provides efficient extraction for the entire spectrum of veterinary drugs, including the difficult classes such as tetracyclines, beta-lactams etc. EMR-Lipid cartridges after extraction provided efficient sample cleanup with easy streamlined protocol and minimal impacts on analytes recovery, improving method reliability and consistency.

Analysis of 76 veterinary pharmaceuticals from 13 classes including aminoglycosides in bovine muscle by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

A multiresidue/multiclass method for the simultaneous determination of 76 veterinary drugs and pharmaceuticals in bovine muscle tissue has been developed and validated according to the requirements of European Commission Decision 2002/657/EC. The analytes belong in 13 different classes, including aminoglycoside antibiotics, whose different physicochemical properties (extremely polar character) render their simultaneous determination with other veterinary drugs quite problematic. The method combines a two-step extraction procedure (extraction with acetonitrile followed by an acidic aqueous buffer extraction) with hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) determination, allowing confirmation and quantification in a single chromatographic run. Further cleanup with solid phase extraction was performed using polymeric SPE cartridges. A thorough ionization study of aminoglycosides was performed in order to increase their sensitivity and significant differences in the abundance of the precursor ions of the analytes were revealed, depending on the composition of the mobile phase tested. Further gradient elution optimization and injection solvent optimization were performed for all target analytes.The method was validated according to the European Commission Decision 2002/657. Quantitative analysis was performed by means of standard addition calibration. Recoveries varied from 37.4% (bromhexine) to 106% (kanamycin) in the lowest validation level and 82% of the compounds showed recovery >70%. Detection capability (CCß) varied from 2.4 (salinomycin) to 1302 (apramycin) µgkg(-1).

Agricultural Applications for Antimicrobials. A Danger to Human Health: An Official Position Statement of the Society of Infectious Diseases Pharmacists.

The use of antibiotics in agriculture, particularly in food-producing animals, is pervasive and represents the overwhelming majority of antibiotic use worldwide. The link between antibiotic use in animals and antibiotic resistance in humans is unequivocal. Transmission can occur by ingesting undercooked meats harboring resistant bacteria, by direct contact of animals by animal handlers, and by various other means. Antibiotics used in aquaculture and antifungals used in horticulture are also an evolving threat to human health. Regulations aimed at decreasing the amount of antibiotics used in food production to limit the development of antibiotic resistance have recently been implemented. However, further action is needed to minimize antibiotic use in agriculture. This article describes the extent of this current problem and serves as the official position of the Society of Infectious Diseases Pharmacists on this urgent threat to human health.

Evaluation of the Most Frequently Prescribed Extemporaneously Compounded Veterinary Medications at a Large Independent Community Pharmacy.

Extemporaneous drug formulation is essential to provide optimal pharmaceutical care to veterinary patients. The need for this is exacerbated by the fact that commercially produced veterinary-specific products, without a human indication, require specialty veterinary manufacturing facilities and a new animal drug application process to gain marketing approval. This study examined the prescription patterns of extemporaneously compounded veterinary preparations in the compounding department at a large independent community pharmacy. Data was obtained from a total of 1348 prescriptions requiring extemporaneous compounding over the course of a two-year period (2014-2015). A database was constructed and each compounded prescription was allocated to a therapeutic category based on the American Hospital Formulary Service Drug Information. Data analysis showed that the most commonly prescribed preparations belonged to the central nervous system (39%), anti-infective agents (21%), and hormones (12%) therapeutic categories. Overall, suspensions were the most dispensed (47%), extemporaneously compounded dosage forms followed by solutions (28%), and capsules (10%). The majority (88%) of compounded preparations were administered by the oral route. The top three drugs that are compounded for veterinary medicine were (1) potassium bromide oral solution for canine epilepsy, (2) methimazole solution used to treat hyperthyroidism in cats, and (3) metronidazole suspension, an antibiotic for the treatment of diarrhea and other infections in dogs and cats. Remarkably, our findings are in good agreement with previously published survey data on the top drugs that are compounded for veterinary medicine. In the era of personalized medicine, veterinary extemporaneous compounding for specialized needs will continue to play an important role providing optimum therapy for veterinary patients.

Developing a systematic approach to ranking residues of veterinary medicines.

This is the last in an occasional series of articles produced for Veterinary Record by the Veterinary Residues Committee(*). It describes a matrix ranking system developed by the committee to provide a systematic approach to ranking residues of veterinary medicines, and some prohibited substances, based on the risk they pose to consumers.

An evidence-based approach to the evaluation of ethnoveterinary medicines against strongyle nematodes of equids.

Cyathostomins are the most important gastrointestinal nematode infecting equids. Their effective control is currently under threat due to widespread resistance to the broad spectrum anthelmintics licenced for use in equids. In response to similar resistance issues in other helminths, there has been increasing interest in alternative control strategies, such as bioactive plant compounds derived from traditional ethnoveterinary treatments. This study used an evidence-based approach to evaluate the potential use of plant extracts from the UK and Ethiopia to treat cyathostomins. Plants were shortlisted based on findings from a literature review and additionally, in Ethiopia, the results of a participatory rural appraisal (PRA) in the Oromia region of the country. Systematic selection criteria were applied to both groups to identify five Ethiopian and four UK plants for in vitro screening. These included Acacia nilotica (L.) Delile, Cucumis prophetarum L., Rumex abyssinicus Jacq., Vernonia amygdalina Delile. and Withania somnifera (L.) Dunal from Ethiopia and Allium sativum L. (garlic), Artemisia absinthium L., Chenopodium album L. and Zingiber officinale Roscoe. (ginger) from the UK. Plant material was collected, dried and milled prior to hydro-alcoholic extraction. Crude extracts were dissolved in distilled water (dH2O) and dimethyl sulfoxide (DMSO), serially diluted and screened for anthelmintic activity in the larval migration inhibition test (LMIT) and the egg hatch test (EHT). Repeated measures ANOVA was used to identify extracts that had a significant effect on larval migration and/or egg hatch, compared to non-treated controls. The median effective concentration (EC-50) for each extract was calculated using PROBIT analysis. Of the Ethiopian extracts A. nilotica, R. abyssinicus and C. prophetarum showed significant anthelmintic activity. Their lowest EC-50 values were 0.18 (confidence interval (CI): 0.1-0.3), 1.1 (CI 0.2-2.2) and 1.1 (CI 0.9-1.4)mg/ml, respectively. All four UK extracts, A. sativum, C. album, Z. officinale and A. absinthium, showed significant anthelmintic activity. Their lowest EC-50 values were 1.1 (CI 0.9-1.3), 2.3 (CI 1.9-2.7) and 0.3 (CI 0.2-0.4)mg/ml, respectively. Extract of A. absinthium had a relatively low efficacy and the data did not accurately fit a PROBIT model for the dose response relationship, thus an EC-50 value was not calculated. Differences in efficacy for each extract were noted, dependent on the assay and solvent used, highlighting the need for a systematic approach to the evaluation of bioactive plant compounds. This study has identified bioactive plant extracts from the UK and Ethiopia which have potential as anthelmintic forages or feed supplements in equids.

Estimation of the use of antibiotics in the small ruminant industry in The Netherlands in 2011 and 2012.

The aim of this study was to estimate the quantity of antibiotics and classes of antibiotics used in the small ruminant industry in the Netherlands in 2011 and 2012. Twelve large veterinary practices, located throughout the Netherlands were selected for this study. All small ruminant farms associated with these practices that had complete records on the quantity of antibiotics prescribed were included. The veterinary practices provided data on all antibiotics prescribed, and the estimated animal used daily dose of antibiotics per year (AUDD/Y) was calculated for each farm. The median AUDD/Y in small ruminant farms was zero in both years (mean 0.60 in 2011, and 0.62 in 2012). The largest quantity of antibiotic use was observed in the professional goat industry (herds of ≥32 goats) with a median AUDD/Y of 1.22 in 2011 and 0.73 in 2012. In the professional sheep industry (flocks of ≥32 sheep), the median AUDD/Y was 0 in 2011 and 0.10 in 2012. In the small scale industry (flocks or herds of <32 sheep or goats), the median AUDD/Y never exceeded 0. The most frequently prescribed antibiotics in the small scale industry and professional sheep farms belonged to the penicillin class. In professional goat farms, antibiotics of the aminoglycoside class were most frequently prescribed. This study provides the first assessment on the quantity of antibiotic use in the small ruminant industry. Given a comparable attitude towards antibiotic use, these results might be valid for small ruminant populations in other north-western European countries as well. The antibiotic use in the small ruminant industry appeared to be low, and is expected to play a minor role in the development of antibiotic resistance. Nevertheless, several major zoonotic bacterial pathogens are associated with the small ruminant industry, and it remains important that antibiotics are used in a prudent way.

An ethnopharmacological assessment of the use of plants against parasitic diseases in humans and animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical surveys are detecting an increasing frequency of exotic plant species in pharmacopeias, which has led researchers to investigate the role of such species in traditional medical systems. According to the diversification hypothesis, exotic species are included to complete pharmacopeias, i.e., to treat diseases for which no native species are known, thus broadening the scope of the plant repertoire. MATERIALS AND METHODS: The present study was conducted at two rural communities in northeastern Brazil aiming at a survey of the plants known or used by the population to treat endo- and ectoparasitic diseases in humans and animals. In addition, plant extracts exhibiting acaricide activity were assessed using the engorged female immersion and larval packet tests (LPT). RESULTS: The results of the present study showed a tendency for native species to be used against ectoparasites and exhibit a broader scope of use compared to exotic species. In turn, exotic species were predominantly indicated to treat diseases caused by endoparasites, although there was an overlap of native and exotic species relative to some therapeutic purpose, e.g., ticks. Only two of the plant species tested exhibited acaricide activity (Nicotiana glauca Graham and Croton blanchetianus Baill.), and in both cases, the activity was weak. CONCLUSION: The ethnobotanical data do not fully support the suggested hypothesis. Overall, the wide versatility of exotic species was not exclusively used to treat parasitic diseases in humans and animals. In addition, the selection of acaricide plants based on the ethnopharmacological study generated uninteresting results.

Simultaneous determination of ß-agonists and psychiatric drugs in feeds by LC-MS-MS.

A method was developed for the simultaneous determination of nine ß-agonists (cimaterol, ractopamine, terbutaline, zilpaterol, salbutamol, clenbuterol, mabuterol, bambuterol and brombuterol) and six psychiatric drugs (diazepam, nitrazepam, oxazepam, chlorpromazine, promethazine and perphenazine) in animal feed by using solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Conditions were optimized for the extraction of the target analytes from animal feed and for clean-up with MCX SPE cartridges. The eluent was evaporated to dryness under nitrogen, and the residue was dissolved in a solution of acetonitrile and 1% formic acid (2:8, v/v) and analyzed by LC-MS-MS using an isotopic internal standard for quantification. Under the optimum conditions, the recovery values of the target analytes were between 70.1 and 110%, with coefficients of variation between 1.9 and 18.4%. The method was very reliable for the simultaneous determination of nine ß-agonists and six psychiatric drugs in animal feed.

Occurrence of steroid hormones and antibiotics in shallow groundwater impacted by livestock waste control facilities.

Wastewater impoundments at concentrated animal feeding operations (CAFOs) represent a potential source of veterinary pharmaceuticals and steroid hormone contamination to shallow groundwater. This study investigates the occurrence of seventeen veterinary pharmaceuticals and thirteen steroid hormones and hormone metabolites in lagoons and adjacent groundwater at operating swine and beef cattle facilities. These sites were chosen because subsurface geology and previous monitoring of nitrate, ammonia and chloride levels in shallow ground water strongly indicated direct infiltration, and as such represent worst cases for ground water contamination by waste water. Pharmaceutical compounds detected in samples obtained from cattle facilities include sulfamerazine; sulfamethazine; erythromycin; monensin; tiamulin; and sulfathiazole. Lincomycin; ractopamine; sulfamethazine; sulfathiazole; erythromycin; tiamulin and sulfadimethoxine were detected in wastewater samples obtained from swine facilities. Steroid hormones were detected less frequently than veterinary pharmaceuticals in this study. Estrone, testosterone, 4-androstenedione, and androsterone were detected in wastewater impoundments at concentrations ranging from 30 to 3600ng/L, while only estrone and testosterone were detected in groundwater samples at concentrations up to 390ng/L. The co-occurrence of veterinary pharmaceutical and steroid hormone contamination in groundwater at these locations and the correlation between pharmaceutical occurrence in lagoon wastewater and hydraulically downgradient groundwater indicates that groundwater underlying some livestock wastewater impoundments is susceptible to contamination by veterinary pharmaceuticals and steroid hormones originating in wastewater lagoons.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2009]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2009.

During the year 2009, 134 reports of suspected adverse drug reactions (ADRs) to veterinary medicinal products (VMPs) were received (106 in the year 2008). The distribution according to species and drug classes remained in line with previous years. Companion animals were involved in most of the reports (46 % dogs, 19 % cats), followed by cattle or calves (22 %). Antiparasitic drugs made the biggest part with 30 % of the reports, followed by antiinfectives (19 %) and hormones (13 %). Some reactions following their use are specifically discussed. 95 additional enquiries about ADRs of VMPs were received by the Swiss Toxicological Information Centre in Zürich. Most of them concerned dogs or cats and antiparasitics or anti-inflammatory drugs. In the vaccinovigilance program, a total of 1020 reports were received, of which 1000 were related to the vaccination against blue tongue disease. The most frequently reported adverse reactions were aborts, mastitis or alterations of milk quality and they are specifically discussed.