Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse

ObjectiveTo describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse.Study designProspective experimental trial.AnimalsEight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg.MethodsMedetomidine (10 μg kg^?1) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis.ResultsPharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL^?1) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg^?1 minute^?1 and a volume of distribution of 1854 ± 565 mL kg^?1. The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL^?1 approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound.Conclusion and clinical relevance Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.     

二氟沙星的研究概况

从结构、制剂、毒理学、药代动力学、药效学、残留与耐药性等方面综述了二氟沙星的研究概况.二氟沙星是畜禽专用的氟喹诺酮类药物,具有良好的理化性能,已开发出注射液和口服液,具有氟喹诺酮类药物类似的毒理学结果,对幼年动物的骨骼有严重影响;口服吸收迅速,组织分布广;对畜禽细菌性疾病和支原体病均有良好的疗效.     

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.     

Pharmacodynamics and pharmacokinetics of tolfenamicacid in ruminating calves: Evaluation in models of acute inflammation

Injections of mild irritants intradermally (carrageenan, zymosan and dextran) and intracaveally (carrageenan)in a tissue cage model of inflammation were used in studies of the pharmacodynamics and pharmacokinetics of tolfenamic acid administered intramuscularly in calves. Inhibition of serum thromboxane (TX) B₂ and inflammatory exudate prostaglandin (PG) E₂ were used as indicators of the magnitude and time course of blockade of cyclo-oxygenase isoforms COX-1 and COX-2, respectively. Single doses of 2, 4 and 8mgkg⁻¹ tolfenamic acid partially inhibited irritant-induced rises in skin temperature (non-dose dependently) and skin oedema (dose-dependently). These doses also markedly inhibited serum TXB₂ synthesis and the duration of inhibition was dose-related. A dose of 2mgkg⁻¹ tolfenamic acid also attenuated skin temperature rise over carrageenan-injected tissue cages, and markedly inhibited exudate PGE₂ synthesis, even though drug penetration into both exudate and tissue cage transudate was limited. Tolfenamic acid pharmacokinetics were characterized by a relatively short t_max (0.94–2.0411), a high estimated Vdarea (1.79–3.20Lkg⁻¹), an estimated ticase 1/2β of 8.01–13.5011 and Cl_β of 0.142–0.175Lkg⁻¹h⁻¹. The actions of tolfenamic acid in inhibiting PGE₂ synthesis and in attenuating two of the cardinal signs of inflammation (heat and swelling) suggest that a dosage of 2mgkg⁻¹ administered intramuscularly should be effective clinically as an anti-inflammatory agent.     

羊肺炎霉形体病研究

１９８０～１９９２年,从四川、云南两省６个种羊场的进口种羊和阿坝、凉山、甘孜州共１０个县的本地绵羊和山羊病肺中分离出２５株霉形体。经理化特性鉴定、药敏试验、致病性测定,并与绵羊肺炎霉形体国际参考株Ｍ·Ｏ·Ｙ９８用生长抑制试验定型,证明这２５株霉形体均为绵羊肺炎霉形体（Ｍｙｃｏｐｌａｓｍａｏｖｉｐｎｅｕｍｏｎｉａｅ）。用微量间接血凝试验（ＩＨＡ）检测,Ｍ·Ｏ·Ｙ９８抗原与丝状霉形体山羊亚种Ｃ８７、丝状霉形体丝状亚种Ｃ８８、羊衣原体、布氏杆菌和羊副结核的抗体均无交叉反应。ＩＨＡ对人工感染羊和有呼吸道症状的自然病例的阳性检出率分别为９５％和８２．６％。试验表明,ＩＨＡ是一种简易、快速而可靠的诊断方法,适用于本病的群体检疫。对人工感染和自然感染发病羔羊进行药物防治试验,证明枝原净效果最好,剂量为每日每公斤体重２２．５ｍｇ,可以抑制肺炎病变的发展。２个试验组的肺炎实变平均值为０．１５±０．２８和０．５８±０．６３,而２个对照组则高达１１．９０±１４．０４和１４．５０±１２．６４。     

几种氟喹诺酮类药物对嗜水气单胞菌体外药效学研究

采用试管两部稀释法测定了盐酸环丙沙星、乳酸环丙沙星、恩诺沙星、单诺沙星、二氟沙星对嗜水气单胞菌的最小抑菌浓度 (MIC)和最小杀菌浓度 (MBC) ,MIC分别是 :0 .0 0 6 2 5 ,0 .0 0 6 2 5 ,0 .0 12 5 ,0 .0 5 ,0 .2 0 ︼g.m L- 1 ,MBC分别是 0 .0 2 5 ,0 .0 2 5 ,0 .0 5 ,0 .10 ,0 .80 ︼g.m L- 1。同时研究了不同药物浓度 (2 MIC,5 MIC,8MIC)对嗜水气单胞菌杀菌的经时变化规律。结果表明 ,这几种药物从 2 MIC到 5 MIC浓度在 3h内菌数减少的 1g值之间差异显著 (P <0 .0 5 ) ,从 5 MIC浓度到 8MIC浓度在 3h内菌数减少的 1g值之间差异不显著 (P >0 .0 5 )     

体外药动学模型中恩诺沙星对猪大肠杆菌的药效研究

为使畜禽专用的喹诺酮类药物更合理地应用,通过建立体外模型的方法,研究了恩诺沙星对大肠杆菌的药效.结果,在消除半衰期为3 h的模型内,2MIC（最小抑茵浓度）的恩诺沙星对猪大肠杆菌仅能抑制4 h,模型运行4 h后细菌出现再生长.5MIC和8MIC的恩诺沙星对猪大肠杆菌可抑制6 h,模型运行6 h后细菌出现再生长.16MIC的恩诺沙星可在模型运行期间对猪大肠杆菌产生持续的抑制杀灭作用.在消除半衰期为6.5 h的模型内,2MIC的恩诺沙星对猪大肠杆菌仅能抑制4 h,模型运行4 h后细菌出现再生长.5MIC、8MIC和16MIC的恩诺沙星可在模型运行期间对猪大肠杆菌产生持续的抑制杀灭作用,4 h已经不能检测到猪大肠杆菌的存在.结果表明,若要使恩诺沙星发挥持续的抗菌效果,保持Cmaz/MIC大于一定数值,同时维持有足够高的AUCo→24/MIC是非常必要的.     

沙拉沙星对实验性猪链球菌病及猪水肿病的药效学

将兽医专用氟喹诺酮类药物沙拉沙星以不同治疗方案分别对实验性猪链球菌病和猪水肿病进行药效学研究。在每天总剂量相同的情况下 ,每天 1次与每天 2次给药取得了较好而相似的疗效 (P>0 .0 5 ) :对猪链球菌病 ,每天总剂量为 10 m g/ kg时 ,肌注给药的治愈率分别为 10 0 %和 90 %,但在迅速改善临床症状方面 ,每天 1次给药优于每天 2次(P<0 .0 5 ) ;对猪水肿病 ,每天总剂量为 5 mg/ kg时 ,肌注给药的治愈率均为 10 0 %。结果表明 ,在总剂量相同时 ,以大剂量、长间隔与以较小剂量、短间隔治疗实验性猪链球菌病与猪水肿病 ,均取得相当的疗效。     

In vitro efficacy and pharmacodynamic profiles of four polyether ionophores against methicillin-resistant Staphylococcus spp.

The objective of this study was to determine the minimum inhibitory concentrations (MICs) and pharmacodynamic profiles of four ionophores (lasalocid, monensin, narasin and salinomycin) against staphylococcal isolates from clinical cases of human and veterinary staphylococcal infections, and to determine the effect of methicillin resistance on the antimicrobial activity of ionophores. Broth microdilution MIC testing was used to determine antimicrobial activity against 156 staphylococcal isolates of human and veterinary origin. Pharmacodynamic profiles were examined using time-kill kinetics profiles against an ATCC type strain of Staphylococcus aureus and a clinical isolate of methicillin-resistant Staphylococcus pseudintermedius. All tests were performed in accordance with CLSI guidelines. All four ionophores demonstrated antimicrobial activity against methicillin-resistant staphylococci at concentrations similar to those observed for methicillin-susceptible isolates of the same species. Testing of human and veterinary MRSA isolates also showed that MIC values were not influenced by the host origin of the isolates. Pharmacodynamic profiles were similar for both isolates tested across all four ionophores, with similar reductions in viable cell counts being observed over an 18- to 24-hr period. Lasalocid, monensin, narasin and salinomycin all demonstrated antimicrobial activity against staphylococcal isolates of human and veterinary origins, with activity being unaffected by methicillin resistance status, although some Staphylococcus species-specific effects were observed that require further investigation.