DrugCentral 2023 extends human clinical data and integrates veterinary drugs.

DrugCentral monitors new drug approvals and standardizes drug information. The current update contains 285 drugs (131 for human use). New additions include: (i) the integration of veterinary drugs (154 for animal use only), (ii) the addition of 66 documented off-label uses and iii) the identification of adverse drug events from pharmacovigilance data for pediatric and geriatric patients. Additional enhancements include chemical substructure searching using SMILES and 'Target Cards' based on UniProt accession codes. Statistics of interests include the following: (i) 60% of the covered drugs are on-market drugs with expired patent and exclusivity coverage, 17% are off-market, and 23% are on-market drugs with active patents and exclusivity coverage; (ii) 59% of the drugs are oral, 33% are parenteral and 18% topical, at the level of the active ingredients; (iii) only 3% of all drugs are for animal use only; however, 61% of the veterinary drugs are also approved for human use; (iv) dogs, cats and horses are by far the most represented target species for veterinary drugs; (v) the physicochemical property profile of animal drugs is very similar to that of human drugs. Use cases include azaperone, the only sedative approved for swine, and ruxolitinib, a Janus kinase inhibitor.

What can we learn from past and recent Bavarian knowledge for the future development of European veterinary herbal medicine? An ethnoveterinary study.

ETHNOPHARMACOLOGICAL RELEVANCE: While the interest in finding medical solutions for the worldwide antibiotics crisis is rising, the legal possibility of simplified authorization of herbal veterinary medicinal products is dwindling. An important basis for both the preservation and development of knowledge in veterinary herbal medicine are pharmacological and clinical studies on the performance of herbal remedies, based on historical written sources on the treatment of farm animals with medicinal plants, as well as current ethnoveterinary research. Nevertheless, there is only limited systematic ethnoveterinary research in Europe, with the exceptions of the Mediterranean region, Switzerland and Austria. We conducted a survey on the ethnoveterinary knowledge of farmers in Bavaria, and analyzed two regional historical textbooks. AIM OF THE STUDY: We documented the local veterinary knowledge about livestock in Bavaria based upon local historical textbooks and upon ethnoveterinary interviews to discover opportunities for the future development of European veterinary herbal medicine. MATERIAL AND METHODS: In 2018/2019 we conducted 77 semi-structured interviews with 101 farmers from different types of farms. Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process, source of knowledge) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers' satisfaction) were collected. To compare our data with the literature, the use reports of two local historical textbooks were analyzed and compared with the data from the interviews. RESULTS: 716 homemade remedy reports (HRs) for altogether 884 use reports (URs) were documented in this study. We picked the 363 HRs that consisted of a single plant species with or without other natural products (HSHRs) for a deeper analysis. These HSHRs were prepared from 108 plant species that belonged to 57 botanical families. The most URs were documented for the families of: Asteraceae, Linaceae and Urticaceae. Calendula officinalis L. (Asteraceae), Linum usitatissimum L. (Linaceae) and Urtica dioica L. (Urticaceae) were the most often documented single species. A total of 448 URs were gathered for the 363 HSHRs. The largest number of URs was for treatments of gastrointestinal disorders and metabolic dysfunctions, followed by skin alterations and sores. For nearly half of the URs the source of knowledge was family and friends. For 80 URs the source of knowledge was different from that of the corresponding HSHRs. For 68% of the URs farmers mentioned at least one use during the last 5 years. Half of the plant species that were mentioned in the historical literature were also mentioned in URs by the interviewees. CONCLUSION: In Bavaria, medicinal plants are actively used by farmers to treat their livestock with a high level of satisfaction. The knowledge is not passed on from generation to generation in a purely static way, but is dynamically developed by the users in almost one fifth of the URs. Ethnoveterinary research combined with data from regional historical textbooks may facilitate pharmacological and clinical studies in veterinary medicine, and the discussion about a simplified registration for traditional herbal veterinary medicinal products.

Pharmacokinetics of cyadox and its main metabolites in rats, pigs, chickens, and carps following oral administration at three dosage.

Cyadox (CYA), a 1,4-dioxide quinoxaline, is a safe and effective antibacterial agent with potential use in food-producing animals. The aim of this study was to compare the pharmacokinetics of CYA (Cy0) and its main metabolites [bisdeoxycyadox (Cy1), 4-desoxycyadox (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), quinoxaline-2-carboxylic acid (Cy6), and 2-hydromethyl-3-hydroxy-quinoxaline (Cy12)] after oral administration at three dosages in pigs, chickens, carps, and rats. The concentration vs. time profile in plasma after single oral administration indicated that CYA was rapidly dissociated into its metabolites and showed the widest distribution in all animals, with the highest apparent volume of distribution. Cy0 and Cy6 persisted for the longest time at lower concentration. Cy1and Cy4 concentration was the highest in pig and rat plasma, while Cy1 was undetectable in chickens, and Cy4 was undetectable in carps following administration at three dosages. Different dosage of the CYX and its metabolites had no significant effect on wash-out period. This study revealed obvious species-specific differences in the kinetic behavior of CYA and its metabolites, which may be related to clinical efficacy and toxicity. Our results would facilitate the judicious use of CYA in different animals.

Toxicologic effect and transcriptome analysis for short-term orally dosed enrofloxacin combined with two veterinary antimicrobials on rat liver.

Presently, toxicological assessment of multiple veterinary antimicrobials has not been performed on mammals. In this study, we assessed the short-term toxicity of enrofloxacin (E) combined with colistin (C) and quinocetone (Q). Young male rats were orally dosed drug mixtures and single drugs in 14 consecutive days, each at the dose of 20, 80, and 400 mg/(kg·BW) for environmental toxicologic study. The results showed that at the high dose treatment, the combination of E + C+Q significantly decreased body intake, lymphocytes count on rats; significantly increased the values of Alanine aminotransferase (ALT), Glutamic oxaloacetic transaminase (AST) and, cholinesterase (CHE); it also got the severest histopathological changes, where sinusoidal congestion and a large number of black particles in sinusoids were observed. This means E + C+Q in the high dose groups was able to cause significant damage to the liver. Other combinations or doses did not induce significant liver damage. Transcriptome analysis was then performed on rats in high dose group for further research. For E + C and E + Q, an amount of 375 and 480 differently expressed genes were filtered out, revealing their possible underlying effect on genomes. For E + C+Q, a weighted gene co-expression network analysis was performed and 96 hub genes were identified to reveal the specific effect induced by this combination. This study indicates that joint toxicity should be taken into consideration when involving the risk assessment of these antimicrobials.

Establishing defined daily doses (DDDs) for antimicrobial agents used in pigs, cattle and poultry in Japan and comparing them with European DDD values.

Monitoring of antimicrobial use is essential in the management of the development and selection of antimicrobial resistance. A variety of indicators has become available to monitor antimicrobial use in human and animal medicine. One of them is an indicator based on defined daily dose (DDD). By using the number of DDDs administered and normalising it by the population at risk of being treated over a defined period, one can estimate the number of treatment days with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values of DDD (DDDvet) for food-producing animals. In this study, we defined Japanese defined daily doses for antimicrobial agents (DDDjp) using DDD values that we previously assigned for antimicrobial products approved for use in pigs, cattle and poultry in Japan and compared them with DDDvet values. For the comparison, the quotient of Japanese and European values (QDDD) was calculated and the effect of the administration route and the number of active substances contained in the preparation was investigated. A total of 59 DDDjp values were defined for 43 antimicrobial agents using the data of 276 products approved for use in pigs. Likewise, a total of 55 DDDjp values were defined for 32 antimicrobial agents using the data of 196 products for use in cattle, and a total of 27 DDDjps values were defined for 25 antimicrobial agents using the data of 131 products approved for use in poultry. A comparison was made for 42, 28 and 17 pairs of DDDjp and DDDvet values for antimicrobial agents used for pigs, cattle and poultry respectively. The comparison showed median QDDD value of 0.61 and 0.66 for antimicrobial agents used for pigs and cattle respectively (p<0.01), indicating that the Japanese daily doses are significantly lower than the corresponding EMA values in these species. For the antimicrobial agents used for poultry, no significant difference was observed between DDDjp and DDDvet values with a median QDDD value of 1.15. The difference between DDDvet and DDDjp values and absence of DDDvet values for some antimicrobial agents marketed in Japan indicate that DDDjp rather than DDDvet should be used as the basis for the calculation of antimicrobial use monitoring in farm animals in Japan.

Evaluation of the antimicrobial use in pigs in Japan using dosage-based indicators.

The use of antimicrobial agents in food-producing animals may lead to the emergence and spread of antimicrobial resistance in bacteria of animal origin. The use of antimicrobial agents in pigs in 2018 in Japan was evaluated in terms of the weight of active ingredient and number of defined daily doses (DDD), using annual sales data of veterinary antimicrobials sold for use in pigs. In addition, the use of antimicrobial agents in the Japanese pig sector in 2008 to 2017 was evaluated to determine whether or not there were any differences in temporal change pattern by use of different metrics. In 2018, 447 metric tons of active ingredient, corresponding to 77,379 × 106 kg-days (Japanese DDD) and 34,903 × 106 kg-days (European DDD) were sold. The proportion of the sales amount of sulfonamides, trimethoprim and lincosamides to the total sales amount was significantly different depending on the metric used. For most antimicrobial classes, the number of Japanese DDDs was greater than the number of European DDDs. These results indicate that the DDD-based metric, which is more reflective of the selective pressure of antimicrobials, is recommended for use in monitoring the antimicrobial use in pigs in Japan. The differences in the number of Japanese DDDs and European DDDs appear to confirm the need for Japanese DDDs.

A preliminary assessment of oral monepantel's tolerability and pharmacokinetics in individuals with treatment-refractory solid tumors.

PURPOSE: Monepantel is an approved veterinary anthelmintic with a strong safety profile. Preclinical evidence suggests novel mTOR pathway-associated anticancer activity. An open-label Phase I trial assessed tolerability, pharmacokinetics, pharmacodynamics and PET-CT imaging following oral Zolvix® monepantel administration to adults with treatment refractory, progressing and unresectable solid tumors. METHODS: Subjects were scheduled to daily home-based monepantel administration for 28 days in a 3 + 3 dose escalation study (5.0, 25.0 and 62.5 mg/kg bw). RESULTS: Of 41 reported drug-related AEs, 68% were Grade 1 and 24% were Grade 2; 35 AEs related to gastrointestinal effects including very poor palatability. DLT and MTD could not be determined due to early termination. Myelosuppression was not observed at the lowest level tested. Three of four Cohort 1 subjects had reduced mTOR pathway marker p-RPS6KB1 levels in PBMCs and achieved RECISTv1.1 SD by CT; one had progressive bony metastases by FDG-PET. One subject recorded PD on day 28, correlating with no detectable plasma monepantel from day 7. Monepantel sulfone dominated monepantel in pharmacokinetics. Both Cohort 2 subjects withdrew early due to AEs and the trial was terminated. CONCLUSIONS: Short-term 5 mg/kg bw monepantel administration provides a combined steady-state trough plasma monepantel and monepantel sulfone concentration of 0.5 µM. Gastrointestinal AEs including very poor palatability are concerning and suggested to be resolved by future drug product reformulation. RECISTv1.1, p-RPS6KB1 and plasma tumor marker outcomes provide preliminary evidence of anticancer activity.

Online availability of fish antibiotics and documented intent for self-medication.

Self-medication and antibiotic utilization without healthcare oversight may lead to delayed appropriate treatment, transmission of communicable infections, untoward adverse events, and contribute to antimicrobial resistance. Previous data suggest people obtain over-the-counter (OTC) animal antibiotics for their personal use. This study examined the availability of OTC fish antibiotics online and the documented intent for self-medication. The authors conducted a web-based cross-sectional study using Google search engine to identify vendor websites selling fish antibiotics in the United States. Vendor websites were included if product information, consumer reviews, and comments were publicly available. Nine fish antibiotics were chosen due to their possibility of having consequences to human misuse. The cost and availability of fish antibiotics was recorded. The proportion of reviews and comments related to human consumption was calculated. Consumer review traffic based on "likes" and "dislikes" received was compared between human- and non-human consumption-related reviews. Selected fish antibiotics were purchased and evaluated for physical appearance and compared to FDA-approved available equivalents. We found 24 website vendors with online ordering available for OTC fish antibiotics. Cost varied significantly by antibiotic and quantity ranging from USD $8.99 to $119.99. There were 2,288 reviews documented for the 9 selected antibiotics being sold. Among consumer reviews, 2.4% were potentially associated with human consumption. Human consumption-related reviews constituted 30.2% of all "likes" received and 37.5% of all "dislikes" received. Human consumption-related reviews received an average of 9.2 likes compared to 0.52 likes for non-human consumption-related reviews. The 8 fish antibiotics purchased were consistent with FDA-approved equivalents in physical appearance. Although infrequent, antibiotics intended for fish use are being purchased online without a prescription for self-medication to circumvent professional medical care. Reviews related to human consumption generate significant online traffic compared to reviews unrelated to human consumption.

Plant and natural product based homemade remedies for veterinary uses by the Peul community in Benin.

ETHNOPHARMACOLOGICAL RELEVANCE: Across Africa, Peul community typically rely on plant-based veterinary knowledge to manage common livestock health problems. Unfortunately, their nomadic life-style being affected by conflicts, land tenure constraints, and drought, they have been shifting to a sedentary life. The process of their settlement led to the erosion of the vast ethnoveterinary skills they had acquired over centuries and forced them to replace the plant and other species they used by commercial products. AIM OF THE STUDY: 1) To collect comprehensive data from the Benin Peul community on common plant-based remedies used to treat livestock diseases and document their preparation and administration. 2) To evaluate the differences and consensus among the Peul community across ecological regions in Benin. MATERIALS AND METHODS: We conducted semi-structured interviews among 88 Peul camps, three (03) bioclimatic zones, and 225 transhumant dialog partners, including agro-pastoralists, healers and pastoralists from mid-July to end of December 2015. Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process) and the corresponding use reports (target animal species, category of use and route of administration) was collected. RESULTS: A total of 418 homemade remedies were reported, of which 235 involved only one plant species (Homemade Single Species Herbal Remedy Reports; HSHR). Information on a total of 310 use reports (UR) were mentioned for the 235 HSHR, and they included 116 plant species belonging to 39 botanical families. Among them, 229 UR were indicated for cattle, 43 UR for poultry, and 38 UR for sheep and goats. The most cited plant species were Khaya senegalensis (19 HSHR; 8.08%), Parkia biglobosa (14 HSHR; 5.95%), Euphorbia unispina (11 HSHR; 4.68%), and Anogeissus leiocarpus (6 HSHR; 2.55%). The URs were indicated for the treatment of viral, parasitic and bacterial diseases but also for multifactorial disorders like diarrhoea, fever, threatened abortion, agalactia etc. The number of plants referred to HSHR decreased from Sudanian to Guineo-congolian zones in concordance with the presence of Peuls. CONCLUSION: The Peul community holds a huge ethnoveterinary knowledge, which needs to be documented, valorised, and promoted. It appears vital to assess phytochemical and pharmacological properties of the most reported species, and their availability across the ecological zones in order to ensure their sustainable use and before this indigenous knowledge disappears completely.

The Impact of Infection and Inflammation on Drug Metabolism, Active Transport, and Systemic Drug Concentrations in Veterinary Species.

Within human medicine, it is recognized that the pharmacokinetics (PK) of many compounds can be altered by the presence of inflammation or infection. Research into the reason for these changes has identified pathways that can influence drug absorption, clearance, and tissue distribution. In contrast, far less is known about these relationships within the framework of veterinary medicine. Rather, most of the PK data generated in veterinary species employs healthy subjects, raising the question of whether these studies are founded on an assumption that healthy animal PK reflect that of the diseased animal population. Accordingly, there is a need to explore the PK changes that might be overlooked in studies that recruit only healthy animals to assesses drug PK. To meet this objective, we surveyed the published literature for studies focusing on the impact of disease on the dose-exposure relationships in food-producing and companion animal species. We found that, consistent with humans and laboratory species, both up- and downregulation of the various cytochrome isoenzymes and/or transporters have occurred in response to an increase in inflammatory mediators. These findings suggest that, as observed in human medicine, the potential for differences in the drug PK in healthy versus animal patients points to a need for acquiring a greater understanding of these changes and how they may influence the dose-exposure-response relationships of veterinary pharmaceuticals. SIGNIFICANCE STATEMENT: This review delivers a much-needed summary of published information that provides insights into how disease and inflammation can influence the appropriateness of extrapolating laboratory-based dose-exposure-response relationships to what will occur in the actual veterinary patient. As part of this review, we also examine some of the method-associated issues to be considered when assessing the reported nature and magnitude of these changes.

[New drugs for horses and production animals in 2019]. / Neue Arzneimittel für Pferde und landwirtschaftliche Nutztiere 2019.

In 2019, one novel pharmaceutical agent for horses or food-producing animals was released on the German market: An injection suspension for horses containing chondrogenic-induced equine allogeneic peripheral blood-derived mesenchymal stem cells as the active ingredient (ArtiCell® Forte) is now available. Two established veterinary active pharmaceutical ingredients became accessible for additional species: a salicylanilide anthelmintic oxyclozanide (Distocur®) for the treatment and control of fascioliasis in sheep as well as a type-I synthetic pyrethroid permethrin (Z-Itch®), which now has additionally been authorized for donkeys. Additionally, one veterinary drug with a new combination of active ingredients (toltrazuril + gleptoferron), 2 drugs (permethrin, omeprazole) in a new pharmaceutical formulation, one drug (lidocaine) with a novel route of administration, one drug (amprolium) with a higher content of the active ingredient, as well as one active substance (butylscopolaminium bromide) in mono-preparation have been launched on the market for horses and food-producing animals.

Advances and challenges in nanocarriers and nanomedicines for veterinary application.

To ensure success in the development and manufacturing of nanomedicines requires forces of an interdisciplinary team that combines medicine, engineering, chemistry, biology, material and pharmaceutical areas. Numerous researches in nanotechnology applied to human health are available in the literature. Althought, the lack of nanotechnology-based pharmaceuticals products for use exclusively in veterinary pharmacotherapy creates a potential area for the development of innovative products, as these animal health studies are still scarce when compared to studies in human pharmacotherapy. Nano-dosage forms can ensure safer and more effective pharmacotherapy for animals and can more be safer for the consumers of livestock products, once they can offer higher selectivity and smaller toxicity associated with lower doses of the drugs. In addition, the development and production of nanomedicines may consolidate the presence of pharmaceutical laboratories in the global market and can generate greater profit in a competitive business environment. To contribute to this scenario, this article provides a review of the main nanocarriers used in nanomedicines for veterinary use, with emphasis on liposomes, nanoemulsions, micelles, lipid nanoparticles, polymeric nanoparticles, mesoporous silica nanoparticles, metallic nanoparticles and dendrimers, and the state of the art of application of these nanocarriers in drug delivery systems to animal use. Finnaly, the major challenges involved in research, scale-up studies, large-scale manufacture, analytical methods for quality assessment, and regulatory aspects of nanomedicines were discussed.

Papel del farmacéutico en la venta y distribución de medicamentos veterinarios / Role of the pharmacist in the sale and distribution of veterinary drugs

El incremento de animales de compañía y animales productores de alimentos, junto con el importante gasto sanitario que estos suponen, hacen que el sector del medicamento veterinario esté adquiriendo cada vez más peso en España. Ante esta situación, se nos plantea la duda de si los propietarios, veterinarios y especialmente farmacéuticos, estamos correctamente preparados e informados. Tal como se observa en la recopilación de leyes sobre venta y distribución de medicamentos de uso veterinario realizada en este trabajo, actualmente no existe una legislación que se adecúe a las necesidades sanitarias de estos animales pudiendo observar en su aplicación intrusiones por parte del veterinario en las funciones legalmente establecidas y propias del farmacéutico o la venta ilegal de medicamentos veterinarios por parte de establecimientos sin la debida autorización. Por lo que al farmacéutico respecta, la falta de información y formación en este campo se manifiesta en varios aspectos como la falta de atención farmacéutica o la aceptación de recetas indebidamente cumplimentadas por el veterinario. Todo ello incrementa el riesgo de realizar un mal uso de los medicamentos por parte del propietario suponiendo así un peligro no solo para el propio animal, sino también para las personas como ocurre en el caso concreto de los antibióticos. Por tanto, nos encontramos frente a un importante problema de regulación y falta de información entre propietarios y profesionales sanitarios, que hace necesaria la realización de campañas informativas y la formación de farmacéuticos y veterinarios desde los Colegios Oficiales y Universidades

The veterinary medicinal sector is gaining more and more importance in Spain because of the increasing of livestock population and pets, and the significant healthcare costs that they involve. Given this situation, are the owners, veterinarians and especially pharmacists, properly prepared and informed? As it can be seen in the compilation of laws about sale and distribution of veterinary medicaments presented in this work, nowadays there is not a legislation adapted to the health requirements of these animals. Indeed, there are some problems in the application of the law such the intrusion of veterinarians in the own and legally established pharmacist’s functions and the ilegal sale of veterinary drugs by non properly authorized establishments. Concerning the pharmacist’s role, the lack of information and training in this area, is manifested in several aspects such a limited ability of pharmaceutical advice and the admission of prescriptions improperly filled by the veterinarian. Taken together, it increases the risk of abuse or wrong use of drugs by the owner, assuming a real danger not only for the animal itself, but also for the people, as in the case of antibiotics consumption. In conclusion, we are facing a critical problem of law regulation and lack of knowledge between owners and healthcare professionals. Therefore, it would be necessary that Universities and Official Colleges carry out information campaigns and organize specific training to pharmacists and veterinarians

A case report of self-medication with over-the-counter fish antibiotic: Implications for pharmacists.

OBJECTIVE: The human use of over-the-counter antibiotics intended for the treatment of pet animals has been recognized as a potential barrier to antibiotic stewardship efforts. The objective of this report is to describe a case of self-medication with a fish antibiotic resulting in delayed medical treatment and provide recommendations for pharmacists practicing in outpatient settings on how to best identify and manage nonprescription antibiotic use. CASE SUMMARY: A 24-year-old man experienced dental pain and "flu-like" symptoms for which he attempted self-treatment with oral amoxicillin 250 mg daily purchased by a family member from a pet store. The amoxicillin was marketed for the treatment of bacterial infection in pet fish. After several days of increasing tooth pain despite the self-medication, the patient presented to an outpatient clinic where he was found to have a molar abscess requiring tooth extraction. The patient responded well to therapy and was counseled to discontinue antibiotic self-treatment. PRACTICE IMPLICATIONS: Undocumented use of nonprescription antibiotics represents a threat to patient safety. Potential deleterious outcomes include resistance, adverse drug events, and delays in definitive infection treatment. Pharmacists should screen patients for nonprescription antibiotic use, provide them counseling on appropriate antibiotic use, and educate other health care professionals on underrecognized sources of nonprescription antibiotics to increase awareness of this growing issue. Furthermore, antibiotic resistance should be considered when recommending an antibiotic agent for the treatment of infections.

[Use of antibiotics in Swiss piglet production and fattening farms]. / Antibiotikaeinsatz in Schweizer Ferkel­erzeugungs- und Mastbetrieben.

INTRODUCTION: In 164 randomly selected Swiss piglet production farms and 101 fattening farms, the indication for antibiotic use in 2012/2013 was recorded and an animal treatment index (TBI) was calculated for each age group. Sows were treated on average 0.9 days per year mainly due to mastitis-metritis-agalactia (MMA). Suckling piglets were treated on average 0.5 days per production cycle, mainly due to diarrhea and polyarthritis. Weaned piglets were treated during 4.4 days, especially due to diarrhea, polyarthritis and wasting. In fattening pigs, treatments were mainly due to diarrhea and HPS-suspicion, and lasted on average 4.8 days. In sows, antibiotics were used prophylactically on 22.6% of the treatment days, in suckling piglets on 50.5%, in weaners on 86.1% and in fattening pigs on 79.0% of the treatment days. A prophylactic oral antibiotic group therapy did not have a significant positive effect on daily weight gain of fattening pigs, nor was it able to reduce the number of individual or group therapies. In farms with prophylactic oral group therapy, the mortality rate during the first two fattening weeks even tended to be higher (p=0.06) than in farms without oral group therapy. Highest priority critically important antibiotics were used in 22.6% of all treatment days in sows, in 37.5% in suckling piglets, in 17.2% in weaned piglets and in 27.3% in fattening pigs. In many farms, antibiotics were not prescribed and used according to the rules of "prudent use".

INTRODUCTION: Dans 164 exploitations suisses de production de porcelets sélectionnées au hasard et 101 exploitations d'engraissement, les données concernant l'utilisation d'antibiotiques en 2012/2013 ont été enregistrées et un indice de traitement des animaux (TBI) a été calculé pour chaque groupe d'âge. Les truies ont été traitées en moyenne 0,9 jour par an, principalement en raison d'une mammite-métrite-agalactie (MMA). Les porcelets allaités ont été traités en moyenne 0,5 jour par cycle de production, principalement en raison de diarrhée et de polyarthrite. Les porcelets sevrés ont été traités pendant 4,4 jours, en particulier en raison de diarrhée, polyarthrite et émaciation. Chez les porcs à l'engrais, les traitements étaient principalement dus à la diarrhée et à la suspicion d'Haemophilus parasuis (HPS) et duraient en moyenne 4,8 jours. Chez les truies, les antibiotiques ont été utilisés à titre prophylactique pendant 22,6% des jours de traitement, chez les porcelets nourris au lait pendant 50,5%, chez les porcelets sevrés pendant 86,1% et chez les porcs à l'engrais pendant 79,0% des jours de traitement. Une antibiothérapie prophylactique de groupe par voie orale n'a pas eu d'effet positif significatif sur la prise de poids quotidienne des porcs à l'engrais et n'a pas permis de réduire le nombre de thérapies individuelles ou de groupe. Dans les exploitations avec traitement prophylactique de groupe par voie orale, le taux de mortalité au cours des deux premières semaines d'engraissement avait même tendance à être plus élevé (p = 0,06) que dans les exploitations sans traitement de groupe par voie orale. Des antibiotiques d'importance critique de haute priorité («Highest priority critically important antibiotics¼) ont été utilisés dans 22,6% de tous les jours de traitement chez les truies, dans 37,5% chez les porcelets allaités, dans 17,2% chez les porcelets sevrés et dans 27,3% chez les porcs à l'engrais. Dans de nombreuses exploitations, les antibiotiques n'étaient pas prescrits ni utilisés conformément aux règles de «l'utilisation prudente¼.

[Assessment of different pain management methods for the treatment of claw lesions in Meat Merino ewes]. / Bewertung verschiedener Methoden des Schmerzmanagements während der Behandlung von Klauenlederhaut-Läsionen bei weiblichen Merinofleischschafen.

OBJECTIVE: Pain management during veterinary procedures is a significant component of animal welfare and has legal as well as ethical implications. Even though regional intravenous anaesthesia (RIVA) is an accepted method for painful procedures involving the distal digits of sheep, this anaesthetic technique is rarely applied in the field. The primary goal was to investigate the feasibility, safety and efficacy of RIVA in sheep. A secondary goal was to examine whether the anaesthetic procedure can be improved by combining RIVA with sedation and whether these methods have a positive effect on the postoperative wellbeing of the animals. METHODS: A total of 36 Meat Merino sheep with contagious interdigital dermatitis and 12 healthy control sheep were used. Behaviour was observed during treatment of the lame sheep using various pain management protocols and during routine claw trimming of the healthy sheep, and all the sheep were observed after the procedures. The observed behaviours were assessed using scores and the scores compared among the animals of the 4 study groups (RIVA, sedation with xylazine hydrochloride + RIVA, placebo, control). RESULTS: RIVA was successfully conducted in sheep. Local reactions at the application sight and in the tourniquet area in 2 animals resolved completely. A significant reduction in defensive movements during the painful procedure confirmed the efficacy of RIVA. Stress-associated behaviours, including head shaking and idle chewing, occurred with a similar frequency in RIVA and placebo animals, leading to the conclusion that stress levels due to the handling in dorsal recumbency were comparable between these 2 groups. Sedation reduced the frequency of pain- and stress-associated behaviours, including guarding, favouring limbs, vocalisation, idle chewing and bruxism. Xylazine hydrochloride-RIVA animals displayed better weight-bearing in the affected limb, better food uptake and ruminated more postoperatively than sheep from the other study groups. CONCLUSION: RIVA in sheep is straightforward, safe and effective. Additional sedation reduces the stress and pain response. This pain and stress management has a positive effect on the postoperative wellbeing of sheep.

Oral group medication in pig production: characterising medicated feed and drinking water systems.

Despite common use of oral group medication in pig rearing, the homogeneity, stability and carry-over of frequently used medicinal products in feed and drinking water are largely unknown. Therefore, a field study was performed on 52 Belgian pig farms, characterising preparation and administration of medicinal products via these systems, and farmers' user experiences with medicated feed and medicated drinking water. The study showed that medicated drinking water is more commonly used than medicated feed, since 90.4 per cent of the farms sometimes use medicated drinking water and 69.2 per cent of the farms sometimes use medicated feed. The drinking water quality is evaluated at least once a year on only 30.7 per cent of the farms. Separate pipelines for medicated and non-medicated circuits were not present in any of the farms using medicated feed and in 27.7 per cent of the farms using medicated drinking water. With drinking water medication, 63.5 per cent of the farmers reported encountering practical problems, often related to solubility issues and precipitation of the active compounds. In contrast, medicated feed is bought ready-to-use from the feed manufacturer in 68.2 per cent of the cases, thus reducing the number of practical problems experienced by the farmer. This study shows room for improvement of oral group treatment, developing appropriate pharmaceutical formulations for drinking water medication, quality control of drinking water, using separate pipeline circuits, and cleaning and disinfecting protocols.

Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration.

Violative chemical residues in animal-derived food products affect food safety globally and have impact on the trade of international agricultural products. The Food Animal Residue Avoidance Databank program has been developing scientific tools to provide appropriate withdrawal interval (WDI) estimations after extralabel drug use in food animals for the past three decades. One of the tools is physiologically based pharmacokinetic (PBPK) modeling, which is a mechanistic-based approach that can be used to predict tissue residues and WDIs. However, PBPK models are complicated and difficult to use by non-modelers. Therefore, a user-friendly PBPK modeling framework is needed to move this field forward. Flunixin was one of the top five violative drug residues identified in the United States from 2010 to 2016. The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in the future and it can be applied to develop new models for other drugs in other food animal species, thereby facilitating the application of PBPK modeling in WDI estimation and food safety assessment.