Summary Background Pyrrolizidine alkaloids are secondary plant metabolites with hepatotoxic effect in humans and several animal species. In recent studies, foods such as herbal teas and honey have been found to be contaminated with pyrrolizidine alkaloids. Objectives The aim of this study was to identify and assess pyrrolizidine alkaloids in compound feeds manufactured for horses and containing either alfalfa or a blend of herbs. Methods Forty‐eight feed products for horses were included in the study. The feedstuffs were analysed for 28 selected pyrrolizidine alkaloids by liquid chromatography‐mass spectrometry. The concentrations of the individual pyrrolizidine alkaloids were summed to calculate the total pyrrolizidine alkaloid content. Results In 7 of 48 samples, pyrrolizidine alkaloid concentrations were below the limit of quantification of 1–5 μg/kg. The median of 41 out of 48 samples was 58 μg/kg, and the 25 and 75th percentiles were 8 and 151 μg/kg. The highest observed pyrrolizidine alkaloid concentrations, 1306 and 1222 μg/kg, were found in two alfalfa‐based feed products, followed by 836 μg/kg in an herb‐containing feed product. Lycopsamine, seneciphylline, seneciphylline‐N‐oxide, senecionine and senecionine‐N‐oxide were the most frequently detected alkaloids. Main limitations Risk assessment was based on no‐observed‐adverse‐effect‐level for pyrrolizidine alkaloids in rats and humans. The specific susceptibility of horses to pyrrolizidine alkaloids remains unknown. Conclusions According to our risk assessment, pyrrolizidine alkaloid contamination should be limited to <90 μg/kg in equine compound feeds. We showed a high rate of pyrrolizidine alkaloids contamination in feed products for horses. In 43% of the analysed samples, pyrrolizidine alkaloid levels exceeded the calculated maximum tolerable levels. There is a need to introduce measures to reduce pyrrolizidine contamination in equine feedstuffs. The Summary is available in Portuguese – see Supporting Information
Based on their performance-enhancing potential, caffeine and theophylline are prohibited substances in equine sports. Residues in horses can be caused by wilful application or by unintended uptake of contaminated feed. The International Federation of Horseracing Authorities recently introduced international residue limits (IRLs) to facilitate the discrimination between pharmacological relevant and irrelevant concentrations in doping samples. The objective of this study was to investigate the scientific validity of these IRLs. A systematic analysis was performed to assess the IRLs by different statistical approaches using published pharmacokinetic data. 31 out of 218 potentially relevant publications met the inclusion criteria. Thereby, both IRLs were found to be appropriate for the exclusion of the presence of a relevant pharmacological effect after a wilful application. The IRL of theophylline was also determined to be suitable for the prevention of positive doping tests caused by the ingestion of contaminated feed. In contrast, the IRL of caffeine is not suitable to prevent positive doping test caused by the ingestion of more than 10 mg caffeine per day per horse with contaminated feed. The lack of corresponding regulation for paraxanthine, a major active metabolite of caffeine and theophylline, was recognised as a substantial shortcoming of the current system, rendering both IRLs incomplete.
Bacterial meningitis in dogs and cats is a rare disease associated with a high lethality rate. The spectrum of causative bacteria includes a diverse set of gram positive, gram negative and anaerobic species. Currently, no veterinary medicinal product is approved for this indication in these species in Europe. The objective of this review was to collect the available pharmacokinetic data for antibiotics approved in dogs and cats to enable a preliminary analysis of their potential effectiveness for the treatment of bacterial meningitis. This analysis yielded data for 13 different antibiotics in dogs and two in cats. Additionally, data about frequently recommended cephalosporines not approved in dogs and cats were included. The collected data was used to assess the potential of the respective antibiotics to attain certain simple pharmacokinetic-pharmacodynamic (PK-PD) indexes in the cerebrospinal fluid (CSF). A more sophisticated investigation using modern methods was not possible due to the limited data available. For this purpose, data about the sensitivity of four bacterial species commonly associated with meningitis in dogs and cats to these antibiotics were included. The analysis provided evidence for the potential effectiveness of ampicillin, doxycycline, enrofloxacin, ceftriaxone and cefoxitin against bacteria frequently detected in bacterial meningitis in dogs. Data were not available or insufficient for the assessment of several antibiotics, including frequently recommended substances like metronidazole and trimethoprim-sulphonamide. Little evidence is available for the use of antibiotics in cats afflicted with this disease, highlighting the need for further research to obtain data for evidence based therapeutic recommendations.
Opioid alkaloids were identified in the urine of horses during an anti-doping control and in a case of intoxication. In both cases, it was suspected that the horses had ingested poppy-contaminated feed. To verify this suspicion, possible opioid alkaloid sources in Germany were identified through a literature research. Additionally, the contaminated feed was botanically and chemically analysed. The results indicated that both cases were most probably caused by the poppy in the feed. This highlights the previously underestimated risk of an intake of poppy-contaminated feed in horses. Recommendations are formulated for the prevention of positive doping-test results and intoxications by poppy-contaminated feeds in horses. Furthermore, a threshold for morphine in urine samples in competing horses is proposed.
ZusammenfassungTierärztinnen und Tierärzte erfüllen als Therapeuten und als Turniertierärzte besonders wichtige Aufgaben bei der Verhinderung von Doping im Pferdesport. Dies setzt umfangreiche und genaue Kenntnisse der Regularien voraus. Zu beachten sind sowohl staatliche Gesetze und Verordnungen, wie z. B. das Arzneimittel- und Tierschutzgesetz, als auch die für den jeweiligen Wettkampf anzuwendenden privatrechtlichen Verbandsregularien. Auf therapeutischer Seite steht der Tierarzt darüber hinaus insbesondere vor dem Problem, korrekte und angemessene Karenzzeiten für legitim angewendete Arzneimittel festzulegen. Dabei lassen sich für einen Teil der in der Pferdemedizin angewendeten Substanzen die von den Pferdesportverbänden veröffentlichten Werte nutzen. Stehen diese nicht zur Verfügung, können ersatzweise Karenzzeiten mithilfe pharmakokinetischer Heuristiken abgeschätzt werden, deren Anwendung in diesem Artikel erläutert wird. Darüber hinaus können Tierärzte bei der Beratung zur Sportpferdefütterung auf mögliche dopingrelevante Futtermittelkontaminanten hinweisen und so zur Vermeidung von Fällen unbeabsichtigten Dopings beitragen. In Mitteleuropa ist hier die Vermeidung botanischer Kontaminationen von Raufuttermitteln durch alkaloidhaltige Pflanzen wie Schlafmohn oder Stechapfel besonders bedeutsam. Turniertierärzten obliegt die Aufgabe der korrekten Probennahme bei der Durchführung von Anti-Doping-Kontrollen. Hierbei müssen Vorsichtsmaßnahmen zur Vermeidung einer Kontamination der Proben beachtet und genaue Abläufe zur Sicherung der Probenidentität und Probenqualität eingehalten werden. Dieses Prozedere wird am Beispiel der Regeln der Deutschen Reiterlichen Vereinigung exemplarisch erläutert.
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