共查询到20条相似文献，搜索用时 125 毫秒
1.
2.
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
3.
4.
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
5.
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
6.
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
7.
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
8.
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
9.
10.
细菌与敏感抗菌药物接触生长繁殖会受到抑制，但当抗菌药物在体内消除后，其效能并不是随着药物的消失而马上消失，在一定时间内，细菌的生长繁殖仍然受到持续的抑制，这种特性就是所谓的抗菌后效应（PAE）。抗菌后效应几乎是所有抗菌药物的共性，也是细菌对药物敏感性的结构特征性指标。临床上使用抗菌药物，大多参考的药效学指标主要是最低抗菌浓度（MIC）和最低杀菌浓度（MBC），这种给药方式忽视了药物与细菌之间的作用过程．忽视了药物对细菌持续抑制的潜力，在药效、毒性、费用上并不是最合理的。虽然目前抗菌后效应在兽医临床上研究还较少．但关注抗菌后效应．对于科学设计用药方案，合理使用各种抗菌药物，以期达到优化使用目标，同样具有重要的临床指导意义。 相似文献
11.
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
12.
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
13.
Lee SH Park HW Kim MJ Noh MH Yoon HS Choi BM Lee EK Noh GJ 《Journal of veterinary pharmacology and therapeutics》2012,35(4):329-341
This study aimed at assessing the predictive performance of a target-controlled infusion (TCI) system, which incorporates canine PK-PD models for microemulsion and long-chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7-day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: -0.8 to 4.9), 18.1% (15.6-20.5), 1.9%/h, 7.3% (5.4-9.3), and -0.5% (-2.6 to 1.6), 8.7% (7.3-10.1), 2.5%/h, 6.0% (4.1-7.2) for microemulsion propofol, and -9.3% (-11.6 to -6.9), 20.1% (18.2-22.0), 5.1%/h, 7.6% (6.1-9.1) and 5.6% (4.1-7.1), 8.0% (6.9-9.3), 4.7%/h, 4.1% (3.1-5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK-PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration. 相似文献
14.
Paulo VM Steagall Ludovic Pelligand Tatiana Giordano Christophe Auberger John W Sear Stelio PL Luna Polly M Taylor 《Veterinary anaesthesia and analgesia》2013,40(1):83-95
ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t1/2ke0 = 47.4 minutes) and receptor binding (kon = 0.011 mL ng?1 minute?1). Persistence of thermal antinociception was due to slow receptor dissociation (t1/2koff = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats. 相似文献
15.
OBJECTIVE: To determine pharmacokinetic-pharmacodynamic (PK-PD) relationships and dose effects for meloxicam in horses and to propose a suitable dosage for use in clinical studies. ANIMALS: 6 adult horses. PROCEDURE: The study was conducted by use of a randomized, Latin-square design. Arthritis was induced in the right carpal joint of each horse by administration of Freund's complete adjuvant. Various dosages of meloxicam (0, 0.25, 0.5, 1.0, and 2.0 mg/kg, IV) were then administered. Validated endpoints including stride length and overall clinical lameness score (scale of 0 to 20) were used to assess the effect of meloxicam. The dose-effect relationship was quantified by use of a maximum possible effect (Emax) model. RESULTS: For stride length (expressed as a relative percentage increase from control values), the median effective dose (ED50) was 0.120 mg/kg for an Emax of 11.15%. For clinical lameness score (expressed as an absolute increase from the control value), the ED50 was 0.265 mg/kg for an Emax of 9.16 units. The PK-PD analysis allowed calculation of a median effective concentration of 130 ng/mL for stride length and 195 ng/mL for lameness score. Use of the Emax model predicted a maximal possible increase in effect of 19.5% for stride length and 13.91 units for lameness score. For stride length and lameness score, the Hill coefficient (slope) was extremely high, which suggested a steep dose-effect relationship. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that meloxicam is a potent anti-inflammatory drug in horses. A dosage of 0.6 mg/kg/d would be appropriate for use in a clinical study. 相似文献
16.
Horwitz E Kagan L Avni-Magen N Daryi D Gati I Hoffman A Friedman M Lavy E 《Journal of veterinary pharmacology and therapeutics》2011,34(5):494-498
Dosage forms of antimicrobials play a critical role in facilitating the attainment of pharmacokinetic-pharmacodynamic (PK-PD) targets as well as adherence in both veterinary and human medicine. The purpose of this study was to develop and evaluate a controlled-release subcutaneous amoxicillin implant for single-dose therapy of large ruminants such as goats, sheep, and deer. The degradable implant, designed to attain PK-PD targets following single administration, was evaluated for amoxicillin release rate and time-concentration profile. In vitro release studies demonstrated constant-rate release of approximately 40% of amoxicillin content within 96 h. In an in vivo study in goats, serving as a model for target animals, a serum concentration of approximately 0.4 mg/L was achieved within 8 h of implant insertion and maintained for >6 days. In comparison, in control goats given a standard single intramuscular amoxicillin dose of 15 mg/kg, amoxicillin peaked at 1.2 mg/L after 1 h, rapidly dropping to below detection level at 8 h. These results suggest that the proposed implant offers a unique modality for animal caregivers to conveniently administer a full antimicrobial course following a single dose of an efficient PK-PD-optimized dosage form. Furthermore, modifications of implant composition may allow for tailoring of its characteristics to various PK, PD, microbiological, and clinical requirements. 相似文献
17.
Haritova AM Rusenova NV Parvanov PR Lashev LD Fink-Gremmels J 《Veterinary research communications》2006,30(7):775-789
Colibacillosis is a systemic disease responsible for important economic losses in poultry breeding; fluoroquinolones, including
danofloxacin, are used to treat diseased animals. The purpose of the present study was to estimate pharmacokinetic–pharmacodynamic
(PK-PD) surrogates for bacteriostasis, bactericidal activity and bacterial elimination against Escherichia coli O78/K80, using a PK-PD approach, for danofloxacin in turkeys after oral administration. Eight healthy turkeys, breed BUT
9, were included in a two-way crossover study. The drug was administered intravenously (i.v.) and orally at a dose rate of
6 mg/kg bw. The values of the elimination half-life and the total body clearance after i.v. administration were 8.64 ± 2.35
h and 586.76 ± 136.67 ml kg-1h-1, respectively. After oral administration, the values of the absolute bioavailability and the elimination half-life were 78.37±
17.35% and 9.74± 2.93 h, respectively. The minimum inhibitory concentration against the investigated strain in turkey serum
was 0.25 μg/ml, four times higher than in broth. The lowest effective ex vivo AUC24/MIC ratios required for bacteriostasis, bactericidal activity, and total killing of E. coliO78/K80 were 0.416 h, 1.9 h and 6.73 h, respectively. The oral dose of 6 mg/kg used in the present study could be interpreted
as being sufficient to eliminate E. coli with an MIC 0.25 μ g/ml. However, considering the demand that antimicrobial resistance should be avoided by complete bacterial
elimination, PK-PD considerations suggest that an even higher dose of 32 mg/kg per day or 0.7 mg/kcal per day should be evaluated
in clinical trials. 相似文献
18.
Saranya Poapolathep Weerapong Laovechprasit Mario Giorgi Somchai Monanunsap Narumol Klangkaew Napasorn Phaochoosak Petcharat Kongchandee Amnart Poapolathep 《Journal of veterinary pharmacology and therapeutics》2020,43(2):215-221
Limited pharmacokinetic information to establish suitable therapeutic plans is available for green sea turtles. Therefore, the present study was conducted to evaluate the pharmacokinetic characteristics of marbofloxacin (MBF) in the green sea turtle, Chelonia mydas, following single intravenous (i.v.) or intramuscular (i.m.) administration at two dosages of 2 and 4 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. MBF in plasma was extracted using liquid–liquid extraction and analyzed by a validated high-performance liquid chromatography (HPLC). MBF was quantifiable from 15 min to 96 hr after i.v. and i.m. administrations at two dose rates. A noncompartmental model was used to fit the plasma concentration of MBF versus time curve for each green sea turtle. The t1/2λz value, similar for both the dosages (22–28 hr), indicated that the overall rate of elimination of MBF in green sea turtles is relatively slow. The average i.m. F% ranged 88%–103%. MBF is a concentration-dependent drug and the AUC/MIC ratio is the best PK/PD predictor for its efficacy. The MBF dosage of 4 mg/kg appeared to produce an appropriate value of the PK-PD surrogate that predicts antibacterial success for disease caused by susceptible bacteria. In contrast, i.m. administration of MBF at a dosage of 2 mg/kg b.w. was not found to produce a suitable PK-PD surrogate index. However, further studies of multiple doses and plasma binding proteins are warranted to confirm an appropriate dosage regimen. 相似文献
19.
20.
Nicole Studer Sabina Diez Bernal Wolfgang Thormann Olivier Levionnois Claudia Spadavecchia 《Veterinary anaesthesia and analgesia》2021,48(3):451-460
ObjectiveTo evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI).Study designProspective, randomized, masked, crossover experimental study.AnimalsA group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)].MethodsLevomethadone 0.1 mg kg–1 or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%–75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05.ResultsHorses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration.Conclusions and Clinical RelevanceA single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α2-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked. 相似文献