Antibiotic prophylaxis in veterinary cancer chemotherapy: A review and recommendations

Bacterial infection following cancer chemotherapy‐induced neutropenia is a serious cause of morbidity and mortality in human and veterinary patients. Antimicrobial prophylaxis is controversial in the human oncology field, as any decreased incidence in bacterial infections is countered by patient adverse effects and increased antimicrobial resistance. Comprehensive guidelines exist to aid human oncologists in prescribing antimicrobial prophylaxis but similar recommendations are not available in veterinary literature. As the veterinarian's role in antimicrobial stewardship is increasingly emphasized, it is vital that veterinary oncologists implement appropriate antimicrobial use. By considering the available human and veterinary literature we present an overview of current clinical practices and are able to suggest recommendations for prophylactic antimicrobial use in veterinary cancer chemotherapy patients.     

Principles of chemotherapy safety procedures

With the ever-increasing demand in veterinary medicine to administer chemotherapy agents, it is imperative for the practitioner as well as the support staff to follow strict guidelines for the administration and disposal of cytotoxic drugs. Because of the possible reproductive risks associated with hazardous drugs, all employees who may be pregnant or trying to become pregnant should be excluded from the process. The long-term occupational effects of these agents are not known; therefore, a standard operating procedure including storage of chemotherapy drugs, protective attire, drug preparation, administration, waste disposal/management, hazardous drug spills, and emergency measures for personal contamination should be carefully implemented and documented.     

Application of risk assessment and management principles to the extralabel use of drugs in food-producing animals

A risk assessment of the food safety implications of drugs used in food-producing animals is an essential component of the regulatory approval process for products containing these drugs. This ensures that there is negligible risk to human health if these drugs are used according to the instructions that appear on the approved label. A relative paucity of approved products for veterinary species; however, forces veterinarians worldwide to use drugs in an extralabel manner to treat disease and alleviate suffering in animals. In food-producing animals, this may result in residues that are potentially harmful to the human consumer. This review describes how risk assessment principles can be extended to evaluate the risks posed by different classes of extralabel drug use. Risk management practices in the United States and Europe are summarized and contrasted to illustrate the application of these principles.     

ACVIM small animal consensus statement on safe use of cytotoxic chemotherapeutics in veterinary practice

The purpose of this report is to offer a consensus opinion of ACVIM oncology diplomates and technicians on the safe use of cytotoxic chemotherapeutics in veterinary practice. The focus is on minimizing harm to the personnel exposed to the drugs: veterinary practitioners, veterinary technicians, veterinary staff, and pet owners. The safety of the patient receiving these drugs is also of paramount importance, but is not addressed in this statement. Much of the information presented is based on national recommendations by Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, United States Pharmacopeia, and other published regulations. These directives reflect an abundance of caution to minimize exposure to medical personnel, but large‐scale studies about the consequences of long‐term occupational exposure are not available in veterinary medicine. Challenges in the delivery of optimal treatment safely and economically to veterinary patients in general practice without access to a veterinary oncologist or other specialist, because of costs or proximity, remain.     

The use of low‐dose metronomic chemotherapy in dogs—insight into a modern cancer field

The era of chemotherapy, which started in the middle of the last century, has been ruled by the routine use of dose‐intense protocols, based on the “maximum‐tolerated dose” concept. By promoting a balance between patient's quality of life and the goal of rapidly killing as many tumour cells as possible, these protocols still play a prominent role in veterinary oncology. However, with the opening of a new millennium, metronomic chemotherapy (MC) started to be considered a possible alternative to traditional dose‐intense chemotherapy. Characterized by a long‐term daily administration of lower doses of cytotoxic drugs, this new modality stands out for its unique combination of effects, namely on neovascularization, immune response and tumour dormancy. This article reviews the rationale for treatment with MC, its mechanism of action and the main studies conducted in veterinary medicine, and discusses the key challenges yet to be solved.     

Liposome‐encapsulated chemotherapy: Current evidence for its use in companion animals

Cytotoxic drugs encapsulated into liposomes were originally designed to increase the anticancer response, while minimizing off‐target adverse effects. The first liposomal chemotherapeutic drug was approved for use in humans more than 20 years ago, and the first publication regarding its use in a canine cancer patient was published shortly thereafter. Regardless, no general application for liposomal cytotoxic drugs has been established in veterinary oncology till now. Due to the popularity of canines as experimental models for pharmacokinetic analyses and toxicity studies, multiple publications exist describing various liposomal drugs in healthy dogs. Also, some evidence for its use in veterinary cancer patients exists, especially in canine lymphoma, canine splenic hemangiosarcoma and feline soft tissue sarcoma, however, the results have not been overwhelming. Reasons for this may be related to inherent issues with the enhanced permeability and retention effect, the tumour phenomenon which liposomal drugs exploit. This effect seems very heterogeneously distributed in the tumour. Also, it is potentially not as ubiquitously occurring as once thought, and it may prove important to select patients for liposomal therapy on an individual, non‐histology‐oriented, basis. Concurrently, new developments with active‐release modified liposomes in experimental models and humans will likely be relevant for veterinary patients as well, and holds the potential to improve the therapeutic response. It, however, does not resolve the other challenges that liposomal chemotherapy faces, and more work still needs to be done to determine which veterinary patients may benefit the most from liposomal chemotherapy.     

P‐Glycoprotein Mediated Drug Interactions in Animals and Humans with Cancer

Drug–drug interactions can cause unanticipated patient morbidity and mortality. The consequences of drug–drug interactions can be especially severe when anticancer drugs are involved because of their narrow therapeutic index. Veterinary clinicians have traditionally been taught that drug–drug interactions result from alterations in drug metabolism, renal excretion or protein binding. More recently, drug–drug interactions resulting from inhibition of P‐glycoprotein‐mediated drug transport have been identified in both human and veterinary patients. Many drugs commonly used in veterinary patients are capable of inhibiting P‐glycoprotein function and thereby causing an interaction that results in severe chemotherapeutic drug toxicity. The intent of this review is to describe the mechanism and clinical implications of drug–drug interactions involving P‐glycoprotein and anticancer drugs. Equipped with this information, veterinarians can prevent serious drug–drug interactions by selecting alternate drugs or adjusting the dose of interacting drugs.     

Potency and stability of compounded cyclophosphamide: a pilot study

Compounding of drugs for use in veterinary oncology is becoming increasingly common. We obtained 15 mg cyclophosphamide capsules from five different compounding pharmacies and performed potency analyses at two time points, as well as stability at 60 days. Potency results for four out of five and zero out of five (4/10) samples analysed were inadequate. Stability at 60 days was acceptable for all but one sample. This pilot study raises several important points of concern when compounding chemotherapy in dogs and cats. Further studies are necessary to solidify this data. Collaboration between pharmacists, veterinarians and regulatory bodies is needed to ensure safe and accurate delivery of compounded drugs to client‐owned animals.     

中国与美国、欧盟、日本和CAC猪组织中兽药残留限量标准的对比研究

为便于中国兽药残留标准的改进和相关法规体系的建立提供参考,同时为中国畜产品贸易提供数据参考,保障人们的饮食安全,促进中国畜产品经济的更好发展,本研究首先对中国新国标GB 31650-2019《食品安全国家标准食品中兽药最大残留限量》中规定的猪组织中兽药残留种类和兽药最大残留限量（MRLs）标准进行了简单分析;然后对美国、欧盟、日本和食品法典委员会（CAC）规定的猪组织中兽药残留种类和兽药MRLs标准与中国新国标进行对比,通过对规定兽药总数、中国没有规定而其他标准有规定的兽药种类、其他标准严于中国标准的兽药种类等几项内容的比较,找出差异。结果显示,中国新国标做出了更加详细的补充和修改;从整体上来看,中国规定的猪组织中兽药MRLs标准越来越完善,大部分标准与欧盟、美国、日本和CAC规定标准的差距也越来越小,然而在部分种类兽药MRLs标准的规定方面和这些国家或组织仍有一定的差距。中国需加强与各个发达国家和组织的交流与合作,推进中国的兽药残留标准的发展,加快对动物产品质量安全标准的更新。     

Mathematical modeling and simulation in animal health – Part II: principles,methods, applications,and value of physiologically based pharmacokinetic modeling in veterinary medicine and food safety assessment

This review provides a tutorial for individuals interested in quantitative veterinary pharmacology and toxicology and offers a basis for establishing guidelines for physiologically based pharmacokinetic (PBPK) model development and application in veterinary medicine. This is important as the application of PBPK modeling in veterinary medicine has evolved over the past two decades. PBPK models can be used to predict drug tissue residues and withdrawal times in food‐producing animals, to estimate chemical concentrations at the site of action and target organ toxicity to aid risk assessment of environmental contaminants and/or drugs in both domestic animals and wildlife, as well as to help design therapeutic regimens for veterinary drugs. This review provides a comprehensive summary of PBPK modeling principles, model development methodology, and the current applications in veterinary medicine, with a focus on predictions of drug tissue residues and withdrawal times in food‐producing animals. The advantages and disadvantages of PBPK modeling compared to other pharmacokinetic modeling approaches (i.e., classical compartmental/noncompartmental modeling, nonlinear mixed‐effects modeling, and interspecies allometric scaling) are further presented. The review finally discusses contemporary challenges and our perspectives on model documentation, evaluation criteria, quality improvement, and offers solutions to increase model acceptance and applications in veterinary pharmacology and toxicology.     

9种抗菌药物对大肠埃希菌最小抑菌浓度的测定

畜禽养殖中会用到一些抗菌药物,而药物选用需要进行药物敏感性试验,目前市售的药敏纸片多为人用抗菌药物,为了制备兽用抗菌药物的药敏纸片,需要对药物的最小抑菌浓度(MIC)进行测定。该研究筛选了国家兽用药物名录中规定的、兽医临床上常用6类共9种抗菌药物(头孢噻呋钠、硫酸链霉素、强力霉素、土霉素、氨苄西林、氟苯尼考、替米考星、硫酸新霉素、青霉素),以大肠埃希菌为指标菌,通过微量肉汤稀释法分别测定了9种常用抗菌药物的最小抑菌浓度(MIC)。结果表明,头孢噻呋钠、硫酸链霉素、强力霉素、土霉素、氨苄西林、氟苯尼考、替米考星、硫酸新霉素、青霉素对指标菌的MIC值分别为为2、4、4、16、8、16、64、32、250μg/mL。研究结果为这些药物的临床应用和药敏纸片的研制提供了基础资料。     

欧盟兽药市场发展动态

本文分析总结了欧盟2009至2019年来以猪、牛、绵羊和山羊养殖为主的畜牧养殖业发展动态及相应的兽药市场销售情况,并从欧盟兽药市场具体情况及其在全球兽药市场的地位角度进行了分析,认为欧盟兽药市场以驱虫药和疫苗为主,抗生素和其他兽药为辅。为国内兽药产业从业者了解欧盟兽药市场,以及国内外兽药产业对比提供了具体数据,有助于对国内外兽药产业进行全面的分析。     

液相色谱-串联质谱法在兽药残留检测中的应用

 随着兽药和药物添加剂在畜禽饲养过程中长期不合理的使用,残留在动物体内的兽药及其添加剂随着食物链进入人体,对人类的健康构成潜在威胁。加强对兽药残留的检测,对保护生态环境和人类的身体健康有着极其重要的现实意义。近年来,液相色谱—串联质谱技术以其良好的适用性、定性定量功能及高灵敏度等优点,在兽药残留的检测方面已得到了广泛应用。论文概述了液相色谱—串联质谱技术在饲料、畜产品和尿液中兽药残留以及违禁药物和有害添加剂检测的应用现状。     

Antibacterial drug resistance and equine practice

The equine practitioner is in a position to make day‐to‐day decisions regarding antimicrobial drug (AMD) use for their patients as well as to educate their clients regarding judicious use. General guidelines regarding judicious use of AMDs in equine patients have been developed by the American Association of Equine Practitioners. Detailed guidelines for AMD use in specific equine diseases supported by clinical trials and results of surveillance studies focused on resistance among equine bacterial pathogens are lacking. Studies that could lead to detailed and justifiable use recommendations would allow the equine practitioner to make more informed decisions regarding when to use AMDs, which drugs should be used and how they should be used (e.g. dose, route and duration).     

畜禽养殖业兽药使用现状及建议

兽药在畜禽养殖中发挥重要作用,但由于养殖户盲目用药,药物选择和使用不规范,随意搭配药物,造成兽药使用量超出安全剂量规定,不仅严重威胁畜禽和人类健康,还污染土壤、水源和大气环境,因此必须对畜禽养殖中的兽药使用进行科学引导和严格规范。该文对我国目前畜禽养殖业兽药使用的现状进行分析,从兽药生产企业准入门槛和销售流通环节入手,结合兽药法律法规、兽药使用规范、兽药监管体系、兽药检测制度提出改善对策。     

A functional model for feline P‐glycoprotein

P‐gp (ABCB1) belongs to the group of export transporters that is expressed in various species at biological barriers. Inhibition of P‐gp can lead to changes in pharmacokinetics of drugs (drug–drug interactions), which can lead to toxicity and adverse side effects. This study aimed to establish a functional assay to measure the inhibitory potential of veterinary drugs on feline P‐gp by means of fluorescence‐associated flow cytometry of feline lymphoma cells. In this model, PSC833 and ivermectin potently inhibited P‐gp function; cyclosporine and verapamil moderately inhibited P‐gp function, whereas ketoconazole, itraconazole, diazepam, and its metabolites had no effect on P‐gp function. This model can be used for testing the inhibitory potency of (new) drugs on feline P‐gp.     

宁夏规模养殖场（园区）兽药使用管理现状调研及规范化管理探讨

为了有的放矢地推进兽药使用管理和确保兽用使用安全,对宁夏省规模养殖场（园区）兽药使用管理的技术力量、兽药贮存条件、兽药来源及贮存方式、兽药使用及休药期执行情况等进行了调查分析,表明规范兽药使用管理已具备有利条件,同时探讨了规范兽药使用管理的主要内容和重点措施。     

Research Process on Design of Liposomes as Drug Delivery System and Its Application in the Field of Veterinary Medicine

As an excellent pharmaceutical carrier,liposomes exhibit characteristics of wide drug loading range,high efficiency and low toxicity.Besides increasing stability and solubility of loading drugs,liposomes can ascribe targeting and sustained release features to loading drugs.Meanwhile,it can improve bioavailability of loading drugs.Based on the above characteristics,liposomes is becoming hot spot of research and application.This article reviewed construction methods of liposomes based on structure,particle design and chosen of preparation method.Combined with application and demands of veterinary medicine,research progress on application of liposome in the field of veterinary medicine was submitted.It is expected that this article will provide reference for the development of new drug delivery systems used in the field of veterinary medicine.     

脂质体递药系统设计思路及其兽药应用研究进展

脂质体作为一种优良的药物载体,具有载药范围广、高效、低毒等特点,能增加包载药物的稳定性和溶解度,赋予药物靶向和缓释的递药特性,并能有效提高药物的生物利用度,是近年来多领域研究和应用的热点。作者从脂质体的结构、粒径设计及制备方法筛选层面总结脂质体的构建思路,结合兽药应用特点和用药需求归纳脂质体递药系统在兽药领域的研究进展,以期为新型递药系统在兽药领域的研发应用提供参考。     

“互联网+”时代下我国兽药产品流通现状及电子商务模式分析

从兽药产品流通领域的困境和互联网+的冲击着手,概述我国兽药产品流通在制度和销售方面的现状、存在的主要问题并分析了原因,通过对电子商务框架和模式的研究阐述了兽药流通领域电子商务的不同交易模式,最后根据兽药产业发展情况和问卷调查分析了现阶段兽药企业电子商务模式的选择,为兽药企业转型电子商务提供参考,为兽药流通领域的变革探寻发展方向。