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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本文概述一种新型动物专用大环内酯类抗生素泰地罗新的理化性质、作用机制、抗菌活性、药动学、药效学、不良反应及残留,为该药开展相关研究、兽医临床的应用提供参考资料。 相似文献
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子宫内膜炎是一种常见的奶牛生殖系统疾病,是造成奶牛不孕的主要原因之一。它严重影响奶牛的繁殖力,给奶牛业造成严重的经济损失。清宫药为纯中药复方制剂,临床上用于治疗和预防奶牛子宫内膜炎,效果显著,为探讨其疗效机理,本试验利用加州兔对清宫药进行了药效学研究。结果显示:与模型组相比,清宫药对实验性急性家兔子宫内膜炎有较好的治疗作用(P﹤0.05)。 相似文献
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我国兽药学10年进展要览 总被引：5，自引：0，他引：5
１９８８—１９９８年,我国兽药学有了迅速的发展。现根据中国畜牧兽医学会兽医药理学及毒理学分会第３～６届学术讨论会共５７８篇论文中有关药学部分内容,作如下综述。１ 药物代谢动力学促进兽用药剂的发展由冯淇辉主持多所院校学者合作对多种抗生素、抗菌药和抗寄生虫药在家畜和家禽体内的药代动力学作了系统研究,编著出版了《兽医药物代谢动力学》和《兽用抗菌药物代谢动力学研究》专著,其试验设计的方法,已由生理模型药动学,进展到病理模型药动学、比较药动学、联合用药药动学、组织器官药动学以及药动学－药效学同步模型等,填… 相似文献
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为研究自制盐酸多西环素注射液在猪体内的药代动力学-药效学,对10头健康猪单次肌内注射盐酸多西环素注射液,采用UPLC法测定血浆中药物浓度,利用药代动力学软件WinNonlin进行数据处理。结果显示,主要药代动力学参数：消除半衰期t1/2为（31．3±9．2）h,达峰时间Tmax为（0．80±0．7）h,峰浓度Cmax为（4132±2475）μg/L,药时曲线下面积AUC为（88378±88095）（μg／L）·h,平均滞留时间MRT为（20．5±2．5）h;PK／PD参数T〉MIC为24h,AUC／MIC〉50。试验表明该制剂以10mg／kg剂量肌内注射,给药间隔两天一次为宜。 相似文献
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常见病原微生物对抗微生物药物的耐药性正逐渐增加,为了达到最佳治疗效果,临床用药必须根据药动学与药效学数据调整给药方案。药动学能够提供药物浓度在组织、体液和感染部位的经时过程,而药效学则反映药物对致病菌的杀灭或抑制能力。蒙特卡罗模拟法则是利用统计学抽样来获得数学方程的近似解的一种方法,目前采用蒙特卡罗模拟法进行实时模拟正成为国际上研究抗微生物药物的药动学和药效学的热点。论文就蒙特卡罗模拟法的原理、拟合过程及其在估算细菌对药物的敏感性折点、比较药动-药效参数以选择最优药物等方面做一综述。 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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Toutain PL Cester CC Haak T Laroute V 《Journal of veterinary pharmacology and therapeutics》2001,24(1):43-55
The present experiment was designed to determine a dosage regimen (dose, interval of administration) in the dog for nimesulide, a nonsteroidal anti-inflammatory drug with in vitro selectivity for the inhibition of cyclo-oxygenase 2 (Cox-2), using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The PK/PD results were compared with those obtained using a classical dose titration study. In the PK/PD experiment, 11 dogs were subjected to Freund's adjuvant arthritis characterized by permanent hyperthermia. Nimesulide (5 mg/kg, oral route) was tested during the secondary phase of the inflammatory response. In the dose titration study, nimesulide (0, 3, 6 and 9 mg/kg, oral route) was tested in eight other dogs using a reversible urate crystal arthritis in a 4-period crossover design. Different PD endpoints (including lameness assessed by force plate and hyperthermia) were regularly measured during the PK/PD experiment, and plasma samples were obtained to determine the plasma nimesulide concentration. The data were modeled using an indirect effect model. The IC50 of nimesulide for lameness was 6.26 +/- 3.01 microg/mL, which was significantly higher than the EC50 value obtained for antipyretic effect (2.72 +/- 1.29 microg/mL). The ED50 estimated from the classical dose titration study were 1.34 mg/kg (lameness) and 3.0 mg/kg (skin temperature). The PK/PD parameters were used to simulate different dosage regimens (dose, interval of administration). The antipyretic and anti-inflammatory effects were calculated from the model for the recommended dosage regimen (5 mg/kg/24 h). It was apparent from this approach, that this dosage regimen enabled 76% of the theoretical maximal drug efficacy to be obtained for pyresis and 43% for lameness. It was concluded from the comparison of in vivo and in vitro IC50, that nimesulide is a potent NSAID for which some Cox-1 inhibition is required to obtain clinically relevant efficacy. 相似文献
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The pharmacokinetic (PK) properties and the pharmacokinetic/pharmacodynamic (PK/PD) relationships for the angiotensin-converting enzyme (ACE) inhibitors (ACEIs), such as enalaprilat, benazeprilat, imidaprilat and ramiprilat, differ from those of conventional drugs. This is because of their immediate and saturable binding to an ACE pool which is partly circulating (and contributing to the measured plasma concentration), and partly noncirculating (tissular), being anchored to the endothelium of vessels and not measurable by the analytical technique. A physiologically based model is required to allow appropriate interpretation of the different phases of the disposition curve of ACEI. The protracted terminal phase observed for all ACEIs is not a conventional elimination phase but a phase dependent on ACEI dissociation from ACE. In contrast, the phase which reflects ACEI elimination (and which is interpreted as a distribution phase for a conventional drug) has a short half-life, thus explaining the absence of drug accumulation during repeated dosing and mild kidney failure. ACE inhibition is the surrogate endpoint generally selected for establishing a PK/PD relationship and for simulating dosage regimen scenarios in order to decide on the appropriate dosage regimen for ACEIs. 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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L. RENARD P. SANDERS M. LAURENTIE J. -M. DELMAS 《Journal of veterinary pharmacology and therapeutics》1996,19(2):95-103
Simultaneous pharmacokinetic-pharmacodynamic (PK/PD) modelling for spiramycin in staphylococcal infections of the mammary gland of cows was used to predict the efficacy of spiramycin. A differential equation derived from the Zhi model was fitted to an in vitro killing curve and post-antibiotic effect determination. A seven-compartment PK model, in which 4 compartments representing each quarter of the mammary gland which was considered to be the effect compartment, was included. The PD model linked to the PK model was able to describe the in vivo spiramycin effect against Staphylococcus aureus . The parameters calculated from in vitro data predicted a rapid decrease for the first 12-24 h, and regrowth within 72 h following the treatment, whereas in vivo the bacterial effect was much less after 24 h than that predicted by the in vitro data. PK/PD modelling permitted the simulation of various doses to optimize the efficacy of the antibiotic, taking into account such dynamic parameters as bacterial growth rate constant, bacterial killing rate constant and the Michaelis-Menten type saturation constant. An optimal dosage regimen of 20 000 IU/kg per day for 3 days was predicted for the treatment of Staphylococcus aureus mastitis. 相似文献
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D. CONCORDET 《Journal of veterinary pharmacology and therapeutics》2006,29(Z1):22-22
There are several means whereby dosage schedules for clinical use may be set, some more appropriate and scientific than others! The challenge of the 21st century must be for colleagues in the pharmaceutical industry, those serving registration bodies and academic colleagues to pool their expertise with the objective of designing dosage schedules for clinical use, which are based on the application of sound scientific principles appropriate for each drug class. In this Roundtable Session colleagues of international standing will review (a) pharmacological and other sources of variability in the responses to drugs; (b) the advantages and limitations of pre‐clinical studies for dose selection; (c) the roles of population PK and population PK/PD together with Monte Carlo simulations in dosage regimen selection; (d) Bayesian approaches to dosage selection and (e) regulatory guidelines on the type and extent of studies required for selecting dosages. There is no unanimity amongst stakeholders on either the principles or the methods underlying dosage schedule design. Dose titration studies have long been the principal means of fixing doses but PK‐PD and population PK‐PD studies are now challenging more traditional approaches. The papers and discussion in this Roundtable Session will provide a critical basis for future advances in this crucial area of therapeutic drug usage. Getting the doses right means that the patient will receive maximum benefit, in terms of optimal efficacy with minimal toxicity, and hence correct dosing will contribute enormously to animal welfare. 相似文献
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Giraudel JM Diquelou A Lees P Toutain PL 《Journal of veterinary pharmacology and therapeutics》2005,28(3):275-285
In laboratory animals many models of inflammation have been developed for preclinical evaluation of the pharmacological profiles of nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, in species of veterinary interest, including the cat, NSAIDs have been studied mainly using dose-titration or dose-confirmation studies in clinical subjects. This is due to the scarcity of appropriate animal models and to the associated lack of quantitative validated endpoints describing the magnitude and time course of drug response. Determination of pharmacokinetic/pharmacodynamic (PK/PD) relationships provides a powerful approach for the selection of effective and safe dosage regimens. In this study, a paw inflammation model in the cat was developed for the preclinical evaluation of NSAIDs using PK/PD modelling. Subcutaneous injection of 500 mg kaolin in the paw produced a well-defined and reproducible inflammatory response that lasted 4-5 days. Several endpoints were assessed for their clinical relevance and for their metrological performance (accuracy and reproducibility). Body temperature, lameness scoring, locomotion tests and possibly skin temperature were the most appropriate endpoints for testing the antipyretic, analgesic and anti-inflammatory effects of NSAIDs in the cat. 相似文献
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Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine,medetomidine, and dexmedetomidine in the horse: a population analysis 
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下载免费PDF全文 K. N. Grimsrud S. Ait‐Oudhia B. P. Durbin‐Johnson D. M. Rocke K. R. Mama M. L. Rezende S. D. Stanley W. J. Jusko 《Journal of veterinary pharmacology and therapeutics》2015,38(1):24-34
The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of the α2‐adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). Population PK/PD analysis was conducted using the Monolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions in HH and HR were found. The drug concentrations required to obtain inhibition at half‐maximal effect (IC50) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration than DEX. The developed models demonstrate the use of mechanistic and mPBPK/PD models for the analysis of clinically obtainable in vivo data. 相似文献