共查询到19条相似文献，搜索用时 250 毫秒
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近年来关于兽用抗菌药物的药代动力学/药效学（Pharmacokinetics/Pharmacodynamics,PK/PD）同步模型的研究取得较大进展。了解PK/PD同步模型的基本概念，利用PK/PD同步模型优化给药方案，可以增强药物的抗菌效果，减少耐药性的发生。该文介绍了PK/PD同步模型的研究方法和应用进展，以及PK/PD同步模型在兽药领域面临的挑战和应用前景，以期提高对兽药PK/PD同步模型及其未来发展趋势的认识，为兽用抗菌药物PK/PD同步模型研究开展提供一定理论基础。 相似文献
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群体药动学及其在兽药监测和评价中的潜在应用 总被引：2，自引：0，他引：2
本文简要介绍了群体药动学的基本概念、群体药动学的各种参数及其意义。概述了群体药代动力学参数的估算方法，并详细描述其代表性方法一非线形混合效应模型（NONMEM）的药理统计学模型和试验设计及数据收集。最后对群体药动学应用于兽医药理学的各个领域的重要意义，包括指导兽医临床用药、监测动物性食品中的药物残留、新药的开发和评价及群体药动－药效同步模型研究等进行了阐述。 相似文献
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抗菌增效剂可以增强抗生素的抗菌活性、减少细菌耐药性的产生、提高治疗效果。药动学研究是临床上制定给药方案,评价药效的重要指标;残留消除研究可以了解药物的残留靶组织、残留标识物,进而制定适宜的休药期。作者简述了艾地普林、甲氧苄啶、二甲氧苄啶3种抗菌增效剂的药动学及残留消除规律,着重对比艾地普林与甲氧苄啶在不同动物体内的药动学参数,显示与甲氧苄啶相比艾地普林具有更长的消除半衰期及更大的表观分布容积,且甲氧苄啶在不同动物体内的消除半衰期差异较大,二甲氧苄啶常作为肠道的抗菌增效剂使用。目前多采用高效液相色谱法及和其他色谱联用的方法,对抗菌增效剂进行药动及残留消除研究,并且也证明了该方法专一性好、灵敏度高。当前由于抗生素的不合理使用甚至滥用导致的药物失效以及细菌耐药性的问题越来越普遍,而抗菌增效剂的出现为解决该类问题提供了新的方向。通过对3种抗菌增效剂在不同动物体内的药动学及残留消除研究,有利于深入了解各种药物在不同动物体内共性和差异性规律,以期发现该类药物在临床使用中存在的问题并且不断地完善抗菌增效剂在临床上的应用。 相似文献
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生理药动学模型是一种模拟机体循环系统的血液流向,将各器官或组织相互联结起来而建立的整体模型,和经典房室模型与统计矩原理相比,生理模型有其独特的优越性.建立药动学生理模型的主要步骤包括收集资料、设计血流图、建立物质平衡方程组、验证和修订模型.目前,国内外学者已开展了数十种化合物在动物或人体内的生理药动学模型研究.生理模型在开展兽医药动-药效模型研究、指导兽药临床合理应用、指导新兽药的研发、评估兽药残留风险等方面具有良好的应用前景. 相似文献
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阐述了兽用抗菌药物群体药动学及药效学的研究历史及现状,并在此基础上提出群体药动-群体药效同步关系正成为兽医药理学研究的一个新方向。 相似文献
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Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine 总被引：1，自引：0，他引：1
In veterinary drug development procedures, pharmacokinetic (PK) and pharmacodynamic (PD) data have generally been established in separate, parallel studies to assist in the design of dosage schedules for subsequent evaluation in clinical trials. This review introduces the concept of PK/PD modelling, an approach in which PK and PD data are generated in the same study, and used to derive numerical values for PD parameters based on drug plasma concentrations. The PD parameters define the efficacy, potency and slope (sensitivity) of the concentration-effect relationship. It is proposed that the parameters derived from PK/PD modelling may be used as an alternative and preferred approach to dose titration studies for selecting rational dosage regimens (both dose and dosing interval) for further evaluation in clinical trials. In PK/PD modelling, the explicative variable for effect is the plasma concentration profile. The PK/PD approach provides several advantages over dose-titration studies, including determination of a projected dosage regimen by investigation of a single dose, in contrast to dose-ranging studies which by definition require testing of multiple dosage. Implementation of PK/PD modelling in the veterinary drug development process is currently constrained by the limited number of veterinary studies performed to date, and the consequently limited understanding of PK/PD concepts and their absence from regulatory authority guidelines. Nevertheless, PK/PD modelling has major potential for rational dosage regimen determination, as it considers and quantifies the two main sources of interspecies variability (PK and PD). It is therefore applicable to interspecies extrapolation and to multiple species drug development. As well as the currently limited appreciation of PK/PD principles in the veterinary scientific community, a further constraint in implementing PK/PD modelling is the need to validate PK/PD approaches and thereby gain confidence in its value by pharmaceutical companies and regulatory authorities. 相似文献
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随着养殖业的迅速发展，兽用抗菌药物的应用越来越广泛，但由于抗菌药物的不合理选择与滥用导致细菌对抗菌药物的耐药率在逐渐提高，几乎所有细菌都获得耐药基因。目前，细菌耐药已成为一个全球性问题，并且临床上，疾病病因复杂，常表现为多种病原菌的继发感染和混合感染，单一用药往往难以有效控制疾病，严重危害养殖业发展。抗菌药物的联合用药可以提升药物的治疗效果，缓解或减少不良反应，降低细菌耐药性发生率，对混合感染或不能进行细菌学诊断的病例，联合用药还可扩大抗菌范围。而药物代谢动力学（PK）与药效学（PD）结合模型可以有效综合药物、机体和致病菌之间的相互关系，为临床提供合理用药方案。因此，作者通过介绍联合用药的优势与问题，抗菌药物PK/PD的分类及PK/PD对联合用药给药方案的优化与指导，总结现阶段兽药抗菌药物联合用药的PK-PD研究进展，以期促进兽医临床抗菌药物的合理使用。 相似文献
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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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Lees P Giraudel J Landoni MF Toutain PL 《Journal of veterinary pharmacology and therapeutics》2004,27(6):491-502
Much useful information relevant to elucidation of mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) at the molecular level can be obtained from integrating pharmacokinetic (PK) and pharmacodynamic (PD) data, such data being obtained usually, although not necessarily, in separate studies. Integrating PK and PD data can also provide a basis for selecting clinically relevant dosing schedules for subsequent evaluation in disease models and clinical trials. The principles underlying and uses of PK-PD integration are illustrated in this review for phenylbutazone in the horse and cow, carprofen and meloxicam in the horse, carprofen and meloxicam in the cat and nimesulide in the dog. In the PK-PD modelling approach for NSAIDs, the PK and PD data are generated (usually though not necessarily) in vivo in the same investigation and then modelled in silico, usually using the integrated effect compartment or indirect response models. Drug effect is classically modelled with the sigmoidal E(max) (Hill) equation to derive PD parameters which define efficacy, potency and sensitivity. The PK-PD modelling approach for NSAIDs can be undertaken at the molecular level using surrogates of inhibition of cyclooxygenase (COX) isoforms (or indeed other enzymes e.g. 5-lipoxygenase). Examples are provided of the generation of PD parameters for several NSAIDs (carprofen, ketoprofen, vedaprofen, flunixin and tolfenamic acid) in species of veterinary interest (horse, calf, sheep and goat), which indicate that all drugs investigated except vedaprofen were non-selective for COX-1 and COX-2 in the four species investigated under the experimental conditions used, vedaprofen being a COX-1 selective NSAID. In these studies, plasma concentration was linked to COX inhibitory action in the biophase using an effect compartment model. Data for S-(+)-ketoprofen have been additionally subjected to inter-species modelling and allometric scaling of both PK and PD parameters. For several species values of four PK parameters were highly correlated with body weight, whilst values for PD parameters based on COX inhibition lacked allometric relationship with body weight. PK-PD modelling of NSAIDs has also been undertaken using clinical end-points and surrogates for clinical end-points in disease models. By measurement of clinically relevant indices in clinically relevant models, data generated for PD parameters have been used to set dosages and dose intervals for evaluation and confirmation in clinical trials. PK-PD modelling of NSAIDs is likely to prove superior to conventional dose titration studies for dosage schedule determination, as it sweeps the whole of the concentration-effect relationship for all animals and therefore permits determination of genuine PD parameters. It also introduces time as a second independent variable thus allowing prediction of dosage interval. Using indirect response models and clinically relevant indices, PD data have been determined for flunixin, phenylbutazone and meloxicam in the horse, nimesulide in the dog and meloxicam in the cat. 相似文献
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McMichael MA Smith SA 《Veterinary clinical pathology / American Society for Veterinary Clinical Pathology》2011,40(2):140-153
Use of viscoelastic point-of-care (POC) coagulation instrumentation is relatively new to veterinary medicine. In human medicine, this technology has recently undergone resurgence owing to its capacity to detect hypercoagulability. The lack of sensitive tests for detecting hypercoagulable states, along with our current understanding of in vivo coagulation, highlights the deficiencies of standard coagulation tests, such as prothrombin and partial thromboplastin times, which are performed on platelet-poor plasma. Viscoelastic coagulation analyzers can provide an assessment of global coagulation, from the beginning of clot formation to fibrinolysis, utilizing whole blood. In people, use of this technology has been reported to improve management of hemostasis during surgery and decrease usage of blood products and is being used as a rapid screen for hypercoagulability. In veterinary medicine, clinical use of viscoelastic technology has been reported in dogs, cats, foals, and adult horses. This article will provide an overview of the technology, reagents and assays, applications in human and veterinary medicine, and limitations of the 3 viscoelastic POC analyzers in clinical use. 相似文献
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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. 相似文献