抗微生物药物PK-PD研究在优化兽药给药方案中的应用

PK-PD模型可用于优化兽药给药方案,制订合理的给药间隔和剂量,在减少细菌耐药性方面有重要意义.本文综述了β-内酰胺类、氨基糖苷类、氟喹诺酮类、大环内酯类等抗微生物药物的PK-PD研究现状,以期为兽药厂家在药物开发、设计合理的剂型与给药方案方面提供依据.     

Review of triazine antiprotozoal drugs used in veterinary medicine

Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.     

兽用抗菌药物群体药动及药效学研究进展

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。     

重庆市兽用抗菌药监管工作之思考

兽用抗菌药物在防治动物疾病、提高养殖效益、保障畜禽产品有效供给中发挥了重要作用,但乱用、滥用、超范围使用兽药和不遵守休药期规定,将导致细菌耐药性产生和兽药残留超标,严重影响畜产品质量安全。本文总结了近两年来重庆市在兽用抗菌药使用监管和减量行动工作中的经验,分析并提出了当前兽药使用监管应当关注和加强的工作重点,以期为兽药监管工作提供参考和借鉴。     

Cross-resistance between antimicrobial agents used in veterinary medicine: molecular background and practical consequences for susceptibility testing

Phenotypic resistance of veterinary pathogens to more than one antimicrobial agent (multi-resistance) may be caused by intrinsic resistance to the antimicrobial agents, acquired cross-resistance, or acquired co-resistance. Known cross-resistances allow to select so-called "representative substances" which are tested and the results of which can also be regarded as being valid for other members of the same class of antimicrobial agents. In general, a limitation in the number of antimicrobial agents to be tested in routine diagnostics is necessary because of capacity and cost efficiency. This is of particular relevance when the broth microdilution method - recommended as the method of choice - with 96-well microtiter plates is used. The knowledge about the relationship between different resistance phenotypes and the corresponding resistance mechanisms is of major value for both, the laboratory personnel and the veterinary practitioner. This review explains how "representative substances" for the most relevant classes of antimicrobial agents used in veterinary medicine are chosen on the basis of known cross-resistances.     

浅谈抗病毒药在兽医上的应用

病毒是危害巨大的病原微生物。由于其独特的生物学特性及不同于细菌的生活和繁殖方式 ,使在病原抑杀和疾病防治上造成困难。本文简要阐述病毒的致病特点及病毒病的防治难点 ,有针对性地介绍和评价国内外曾在动物病毒病中应用过的若干药物。旨在为国内兽医界在抗病毒药的科学研究和规范开发上提供一些线索和资料     

兽药制剂新工艺开发过程中相关问题的探讨

对兽药制剂新工艺开发过程中所面临的产品安全性、有效性、设备要求、检测方法的建立、产品的价格及市场接受程度等问题进行了探讨,以期为兽药制剂新工艺的开发提供参考。     

The current antimicrobial resistance situation in Swiss veterinary medicine]

Antimicrobial susceptibility data (n = 1501) and bacterial isolates (n = 258) of important bacterial pathogens from animals were collected in collaboration with eight Swiss laboratories from May 1999 to February 2000. Using these data, the antimicrobial resistance situation could be assessed for the following bacterial species: Escherichia coli, Salmonella, Haemophilus parasuis, Actinobacillus pleuropneumoniae, Pasteurella multocida, Mannheimia haemolytica, Bordetella bronchiseptica, Campylobacter jejuni, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus intermedius, Streptococci, and enterococci. Differences in the distribution of resistance between animal species could be evidenced in E. coli and salmonella. Some resistance frequency data were compared with those obtained in 1980. A significant increase of resistance frequency was observed for several antibiotics. This includes in particular an increase of ampicillin, gentamicin, and cotrimoxazole resistance in E. coli. A similar increase was observed in salmonella for ampicillin, streptomycin, sulfonamides, and nalidixic acid. Staphylococci from dogs (S. intermedius and S. aureus) also presented a clear increase of resistance for penicillin, neomycin, sulfonamides, cotrimoxazole, and erythromycin. Finally, a comparison with data from abroad shows that the antibiotic resistance situation in Switzerland is relatively favorable.     

Obligate anaerobes in clinical veterinary medicine: susceptibility to antimicrobial agents

Ninety-nine isolates of obligate anaerobic bacteria obtained from clinical material were tested for susceptibility to ten antimicrobial agents. Regardless of the species of animal from which the isolates were obtained 90–95% were inhibited by ≤4 μg of ampicillin/ml, ≤4 μg of chloramphenicol/ml, ≤1 μg clindamycin/ml, ≤2 μg metronidazole/ml, ≤8 μg minocycline/ml, ≤16 μg penicillin Gyml, and ≤16 μg tetracycline/ml. All the aminoglycoside antibiotics tested (gentamicin, kanamycin, neomycin, and streptomycin) were shown to be relatively ineffective requiring ≥128 μg/ml for the inhibition of >50%of the isolates. The minimal inhibitory concentration of penicillin G and tetracycline tended to be higher for isolates from non-human primates (penicillin G) and ruminants (tetracycline).     

PK-PD结合模型及其在兽用抗菌药研究中的应用

随着PK-PD结合模型的发展,其在兽用抗菌药中的应用研究也受到了高度重视。本文通过对PK-PD结合模型理论的阐述,根据抗菌药物参数,对各类抗菌药物给药方案的制订作一简要分析,以期对优化临床给药方案和促进抗菌药物的临床合理使用有所帮助。     

Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine

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.     

推行《兽药GMP》是兽药企业的必然选择——董义春处长在兽药GMP实施运行情况座谈会上的讲话摘要

推行《兽药GMP》是重整兽药生产资源,实现跨越式发展,提升市场竞争能力的必然选择,那种认为“搞GMP,先搞的先死,后搞的后死,不搞的等死”的观点是错误的。2005年12月31日是最后期限,到时候达不到GMP要求的企业肯定要被“摘牌”。任何企业不要有任何侥幸心理,观望是没有出路的。加强兽药企业管理工作的核心内容就是推行《兽药GMP》,推行《兽药GMP》只是在整个行业中首先推行的一个针对生产环节的标准,以后还准备推行别的标准,如GLP、GSP等,使整个兽药研究环节、生产环节、经营环节、使用环节都朝着良好的规范方面努力。整顿和规范市…