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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 
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下载免费PDF全文 Z. Lin R. Gehring J. P. Mochel T. Lavé J. E. Riviere 《Journal of veterinary pharmacology and therapeutics》2016,39(5):421-438
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. 相似文献
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J. M. Bermudez A. G. Cid M. V. Ramírez‐Rigo D. Quinteros A. Simonazzi S. Snchez Bruni S. Palma 《Journal of veterinary pharmacology and therapeutics》2014,37(2):105-124
An important frontier in the administration of therapeutic drugs to veterinary species is the use of different polymers as drug delivery platforms. The usefulness of polymers as platforms for the administration of pharmaceutical and agricultural agents has been clearly recognized in the recent decades. The chemical versatility of polymers and the wide range of developed controlled‐release strategies enhance the possibilities for the formulation of active molecules. In particular, the veterinary area offers opportunities for the development of novel controlled‐release drug delivery technologies adapted to livestock or companion animal health needs. In some cases, it also allows to improve profitability in meat production or to meet the safety criteria related to drug residues. A number of factors affect the selection of polymers and subsequent properties of the controlled‐release drug delivery system. However, their selection also dictates the release kinetics of the drug from the delivery system. Such choices are therefore crucial as they affect the success and potential of the delivery system for achieving the therapeutic goals of the veterinarian. It is the intention of this review to give an overview of the most relevant polymers, which are used or have been tested as drug delivery release rate modifiers in the veterinary field. The article highlights some recent developments focusing on their advantages and applications and analyzes the future direction of the scientific and technological advancements in this area. 相似文献
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Chauvin C Madec F Guittet M Sanders P 《Journal of veterinary pharmacology and therapeutics》2002,25(6):455-459
Pharmaco-epidemiology, which has emerged within the last 20 years as a new discipline in human medicine, deals with the quantities of drugs consumed and their effects on populations in terms of epidemiological concepts and tools. To a lesser extent, it is also practised in veterinary medicine. The applications presented in this review are illustrative of pharmaco-epidemiological and -economical concepts. Assessment of drug consumption, the study of adverse drug effects, and the economic implications of drug use are the three main fields considered. Developments can be expected in veterinary medicine within the next few years relative to novel areas of interest such as antimicrobial resistance and new therapeutic class uses. These applications will require methodological progress and the elimination of current gaps. Pharmaco-epidemiological methods need to be developed, which implies close co-operation between statisticians, pharmacologists, veterinary practitioners and epidemiologists. A greater use of the term 'pharmaco-epidemiology' as a keyword in literature would facilitate recognition of this domain which associates closely epidemiology and pharmacology. 相似文献
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Kochevar DT 《Journal of veterinary medical education》2003,30(4):331-337
Veterinary clinical pharmacology encompasses all interactions between drugs and animals and applies basic and clinical knowledge to improve rational drug use and patient outcomes. Veterinary pharmacology instructors set educational goals and objectives that, when mastered by students, lead to improved animal health. The special needs of pharmacology instruction include establishing a functional interface between basic and clinical knowledge, managing a large quantity of information, and mastering quantitative skills essential to successful drug administration and analysis of drug action. In the present study, a survey was conducted to determine the extent to which veterinary pharmacology instructors utilize information technology (IT) in their teaching. Several IT categories were investigated, including Web-based instructional aids, stand-alone pharmacology software, interactive videoconferencing, databases, personal digital assistants (PDAs), and e-book applications. Currently IT plays a largely ancillary role in pharmacology instruction. IT use is being expanded primarily through the efforts of two veterinary professional pharmacology groups, the American College of Veterinary Clinical Pharmacology (ACVCP) and the American Academy of Veterinary Pharmacology and Therapeutics (AAVPT). The long-term outcome of improved IT use in pharmacology instruction should be to support the larger educational mission of active learning and problem solving. Creation of high-quality IT resources that promote this goal has the potential to improve veterinary pharmacology instruction within and across institutions. 相似文献
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兽药(含饲料药剂)是实现现代养殖的物质基础。本文通过2009与2011年全国10次和11次兽医药理毒理学术研讨会的论文[1,2]综述,介绍兽医药学科技近年研究与应用进展,分为:重要主题,基础药理与临床治疗学,兽药代谢动力学与药物残留,抗菌药与细菌耐药性,中草药及化药新剂型新制剂的研发等5部分。 相似文献
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Sharon M Gwaltney-Brant Wilson K Rumbeiha 《Veterinary Clinics of North America: Small Animal Practice》2002,32(2):323-339
Although the availability of an antidote for a toxic agent does not take away the primary responsibility of the clinician to manage the patient's clinical signs, the use of antidotes in appropriate situations can result in a more rapid recovery with potentially fewer long-term complications. Recent advances in pharmacology and molecular biology have resulted in the development of new and safer antidotal therapies for the management of toxicosis. The progress in immunotoxicotherapy over the last two decades continues and may ultimately lead to an era when the clinical toxicologist has a vast array of antibody fragments available for use with specific toxic agents. Development of specific pharmacologic antagonists for other agents should also enable the clinician to more reliably manage toxicoses. In spite of all these potential advances, the management of most toxicoses still relies on the application of sound veterinary medical principles. 相似文献
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J P Griffiths 《Veterinary Clinics of North America: Small Animal Practice》1988,18(6):1243-1265
Drug interactions are often the result of complex biochemical, physical, and kinetic factors and may not often be easily predicted or even recognized. Although this article has attempted to point out the more common mechanisms and results of drug interactions, the few interactions that have been documented in small animals are undoubtedly only the tip of the iceberg. For the safety of patients and for the highest quality of veterinary care, it is essential that the practitioner become thoroughly familiar with the actions and interactions of drugs used in his or her practice and realize the possible consequences of multiple drug therapies before adding another drug to a therapeutic regimen. From a therapeutics standpoint, the temptation to polypharmacy is great, but the adage "an ounce of prevention is worth a pound of cure" is especially appropriate when discussing drug therapy. The rational decision to use as few drugs as possible in any given situation is the route to safe and successful drug therapy. 相似文献
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新型药物递送系统在新药研发中的应用近年来在国内外受到了广泛的重视。兽用新型载药系统的研究,解决了兽用药物在动物体内半衰期短、靶向性差、药物利用率低以及药物溶解性特定要求等问题,可开发出新型、高效、安全的生物药物剂型。兽药新型递药系统已在兽药领域展现出广阔的前景,并成为兽药研发的新方向之一。本文就目前主要递药系统(如缓控释递药系统、纳米递药系统、靶向给药系统、透皮给药系统、生物粘附给药系统、植入控释给药系统以及自乳化给药系统等)在兽药制剂领域的研究进展进行综述,并分析和探讨了新型递药系统在兽医领域应用瓶颈、现有研究面临的挑战及未来的发展趋势,以期为新型递药系统在兽药领域的应用提供参考。 相似文献
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L. A. Wittenburg D. H. Thamm D. L. Gustafson 《Veterinary and comparative oncology》2014,12(2):114-119
Understanding the relationship between drug dose and exposure (pharmacokinetics, PK) and the relationship between exposure and effect (pharmacodynamics) is an important component of pharmacology when attempting to predict clinical effects of anticancer drugs. PK studies can provide a better understanding of these relationships; however, they often involve intensive sampling over an extended period of time, resulting in increased cost and decreased compliance. Doxorubicin (DOX), one of the most widely used antineoplastic agents in veterinary cancer therapy, is characterized by large interpatient variability in overall drug exposure and the development and degree of myelosuppression following equivalent dosages. We have developed and validated a limited‐sampling strategy for DOX, in which three blood samples are obtained over 1 h post‐treatment, that accurately predicts patient exposure. This strategy could allow for refining of dosing variables and utilization of therapeutic drug monitoring to ensure optimized dosing. 相似文献
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An increase in the incidence of severe, invasive, systemic fungal infections has been noted over the last decade in human and veterinary medicine. Reports of drug resistance and therapeutic failure to currently available antifungal agents have also been on the rise. Many factors are likely to be involved in these trends, including immune suppression and the use of broad-spectrum antibiotics. The use of fungistatic drugs, suboptimal doses, compounded drugs, poorly absorbed drug formulations, and inadequate tissue penetrations of antifungals also contribute to the development of acquired resistance. Because of the unique chemical complexities of the antifungal agents, drug/drug and drug/food interactions may also play a significant role in poor therapeutic outcome. This review summarizes the pharmacology and toxicology of the antifungal agents in current use for systemic mycosis and introduces some of the newer antifungal agents that anecdotally show very promising results. 相似文献
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van Miert AS 《The Veterinary quarterly》2000,22(1):3-11
Veterinary pharmacology has undergone a gradual development in the Netherlands during this century. Starting from a historical perspective the paper aims to provide an overview of future trends and important issues in the area of veterinary pharmacology and toxicology. It is pointed out that this discipline comprises several subdisciplines as the comparative aspect of both, pharmacology and toxicology, is inherent to veterinary medicine which has to address a broad variety of animal species. Thus, the comparison of drug effects, side effects, and drug disposition as well as the comparison of the species-specific susceptibility to xenobiotics are obvious challenges in this discipline. Several areas in clinical pharmacology are highlighted to indicate future research needs. Finally, the principles of Good Veterinary Practice are presented as the 'golden standard' in veterinary clinical pharmacology. 相似文献
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Signal transduction in inflammatory processes, current and future therapeutic targets: a mini review
The selective control of inflammatory reactions will continue to be a major issue in the development of new drugs. Many new molecular targets are coming up. This paper highlights a few key mediators that are nowadays considered as interesting therapeutic intervention points. Cytokines play an important regulatory role in the initiation, maintenance and termination of inflammatory reactions. More than 50 cytokines have been identified, and more and more has become known about their receptors and signal transduction pathways. Tumour necrosis factor-alpha (TNF-alpha) is still regarded as one of the initial cytokines of the cascade, and different approaches are followed to control its synthesis, release or effects. Lipopolysaccharide (LPS) is a one of the triggers that is able to induce a strong TNF-response. Inhibitors of cyclic nucleotide phosphodiesterases (PDEs), including rolipram and pentoxifylline suppress the LPS-induced TNF-alpha production in monocytes/macrophages. In our laboratory it has been shown that the alternative way to increase cAMP levels, via stimulation of beta-adrenergic receptors, also provides an effective way, both in vitro and in vivo, to inhibit TNF-alpha release. Other therapeutic ways include the use of antibodies directed to cytokines, TNF receptor fused to IgG, antibody therapy against TNF, the use of MAP kinase inhibitors. The different signal transduction pathways, including the NF-kappa B activation route may provide alternative pharmacological tools. We may surely expect anti-inflammatory drugs of much greater specificity to be developed in the next decade. Despite the relative limited investments in veterinary drug development this will also have consequences for veterinary therapy. 相似文献
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B. H. Ali 《Veterinary research communications》1988,12(1):67-75
Specific recommendations for drug dosages for the camel are rare and doses for this species are usually extrapolated from those recommended for other species. The pharmacology and toxicity of drugs likely to be used in the camel needs to be further studied to ensure the efficacy and safety of these drugs in this species.Most of the reported work is on the chemotherapeutic efficacy of a few drugs long in use in other species against trypanosomiasis, mange and gastrointestinal nematodes. Areas of study most deficient are pharmacodynamics, pharmacokinetics and drug metabolism. The anatomical, physiological and biochemical peculiarities of the camel warrant more pharmacological and toxicological studies in this species.This article surveys the literature on the pharmacology, toxicity and therapeutic uses of some antiparasitic and antibacterial drugs and central nervous system depressants commonly used in the camel. It appears that camels are more susceptible to the toxic action of some trypanocidal drugs than other species. In certain cases they may metabolize some drugs differently. In general, the camel appears to be a good subject for analgesics and anaesthetics. 相似文献
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Radiation therapy has been used to treat animal cancers for more than 100 years. Clinical experiences and experimental results have been widely published and provide a basis for the recognition of radiation therapy as an integral component of multimodal cancer management in veterinary oncology. As the expectations of pet owners and the demand for treatment of companion animals with cancer have increased, veterinary oncology itself has undergone dramatic advances in the past several decades both in terms of improved diagnostics and treatments, including increased accessibility of radiation therapy. Synchronous with development of the specialism of veterinary radiation oncology, confusion and controversy have arisen with regard to distinguishing between different types of radiotherapy and methods of treatment delivery. Importantly, the confusion extends beyond semantics, and includes opinionated debate about defining which forms of therapy (if any at all) are optimal for a given patient. This exemplifies how, despite marks of maturity including age and a robust publication history, the field of veterinary radiation oncology is in some ways still in its infancy. The purpose of this article is to review the evidence base for daily (fine) fractionation versus weekly (coarse) hypofractionation in veterinary oncology, using selected tumour types as examples. 相似文献
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K.L. Mealey J. Fidel 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2015,29(1):1-6
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. 相似文献
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Blood gas analysis. 总被引：3，自引：0，他引：3
Thomas K Day 《Veterinary Clinics of North America: Small Animal Practice》2002,32(5):1031-1048
Evaluation of both arterial and central venous blood can be valuable in monitoring the critically ill veterinary patient. The traditional approach, which concentrates on arterial blood analysis only, may miss important aspects of oxygen delivery to tissues, especially in patients with poor perfusion. The advances that have resulted in affordable bedside blood gas analyzers have created a clinical situation in which blood gas analysis should be an integral part of critical care monitoring. Following basic principles of interpretation, blood gas analysis, which has traditionally been viewed as a complex method of monitoring, should become more useful. Assessing both the arterial and central venous samples should result in more efficient and higher quality care for veterinary patients. 相似文献