Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves

The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.     

内酯类新抗生素泰拉霉素的研究进展

泰拉霉素是动物专用半合成大环内酯类抗生素,对于防治猪和牛的呼吸系统疾病疗效确切。从泰拉霉素的理化性质、作用机制、抗菌活性、药动学和药效学、急慢性毒性及药物残留等方面进行综述,旨在为该药在兽医临床应用提供参考资料。     

米诺沙星在中国对虾体内的代谢动力学及在养殖系统中的消除

[目的]为米诺沙星在中国对虾养殖中的合理应用及环境安全提供理论依据。[方法]在水温21~22℃条件下,米诺沙星药饵以每天30 mg/kg虾体重连续投喂中国对虾5 d后,应用反相高效液相色谱法(RP-HPLC)研究米诺沙星在中国对虾体内的代谢动力学以及米诺沙星在水环境及底泥环境中的分布和消除。[结果]试验结果表明:试验数据经3P87药动学软件分析,米诺沙星在中国对虾各组织中的代谢符合开放性二室模型。药饵给药后,大部分药物经饵料被对虾摄食,小部分的米诺沙星进入环境中,随着时间的推移,米诺沙星在水环境中的含量逐渐衰减,在同一时间时距离表层水面10 cm处与距离底泥表面10 cm处的水样样品含量在0.05水平无差异。水体中的米诺沙星的含量-时间拟合曲线回归方程为Y=-0.002 9lnX+0.008 6。[结论]底泥对米诺沙星有吸附作用,米诺沙星有向底泥转移的趋势。     

Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats.

METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two–treatment, two-period study. Alfaxalone at a dose of 5?mg/kg was administered either I/V or I/M. Blood samples were collected between 2–480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5–120 minutes after drug administration using a numerical rating scale (from 0–18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded.

RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5–15 minutes after I/V administration and deep sedation (scores 11–15) at 20 and 30 minutes. Deep sedation was observed from 10–45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery.

CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.     

药物代谢动力学猪链球菌病模型的研制

为研制适于猪的药物代谢动力学研究的传染病模型，取长白×杜洛克杂种猪１６头（体重３２．０±０．７ｋｇ），每猪皮下接种纯净猪链球菌（Ｃ７４－４１型）１２．５亿个活菌，复制出典型的亚急性型猪链球菌病。动物经感染后１ｄ体温持续升高１．５～２．０℃。血浆总蛋白含量开始持续降低（Ｐ＜０．０１），血清肌酐浓度则开始升高（Ｐ＜０．０５）。感染后２．５ｄ，磺溴酞的消除半衰期和给药后１５ｍｉｎ的滞留率均下降（Ｐ＜０．     

Influence of oral co-administration of a preparation containing calcium and magnesium and food on enrofloxacin pharmacokinetics

The objective of this study has been to determine the influence of food and ions on the pharmacokinetics of enrofloxacin (ENRO) in turkeys, administered per os at a dose of 10 mg/kg of body weight (b.w.). Co-administration of ENRO with ions or with food significantly retarded its absorption, and the interaction was more pronounced when the drug was given together with food. The bioavailability of ENRO was 65.78 ± 7.81% and 47.99 ± 9.48% with ions and food, respectively. The maximum concentration (C_max) in plasma of animals exposed to ions reached 0.87 ± 0.26 μg/ml in a t_max of 2.07 ± 0.76 h; in animals which were fed while medicated, the analogous parameters were 0.36 ± 0.13 μg/ml and 8.06 ± 3.08 h. The PK/PD analysis demonstrated that a decrease in the concentration of ENRO in turkeys’ blood due to the interaction with ions or food might impair the drug's clinical efficacy toward some pathogenic microorganisms in turkeys if a routine dose of 10 mg ENRO/kg b.w. is administered.     

硫酸多粘菌素E在猪体内的药代动力学和生物利用度研究

健康断奶仔猪 5头 ,分别进行单剂量肌注 (2 5和 5 0mg/kgb .w .)和静注 (2 5mg/kgb .w .)给药 ,并用微生物学方法对硫酸多粘菌素E在猪体内的药代动力学和绝对生物利用度进行了研究。以 3P97程序处理血药浓度—时间数据 ,结果表明 ,以 2 5和 5 0mg/kgb .w .的剂量肌注给药时 ,其血清中药物的峰浓度 (Cmax)分别为 3 73± 0 2 8μg/ml和 6 40± 0 1 8μg/ml,达峰时间分别为 32 2 2± 1 51min和 34 1 8± 1 76min ,消除半衰期 (t1 / 2 β)为 2 55 99± 1 3 65min和 2 64 0 8± 2 8 57min ;以 2 5mg/kgb .w .的剂量静注给药时 ,其消除半衰期 (t1 / 2 β)为 2 51 2 8± 1 2 53min。静注和肌注在体内的分布均为一级吸收二室模型。肌注 2 5和 5 0mg/kgb .w .剂量的注射液时 ,其平均绝对生物利用度分别为 98 30 %和 88 54 %。     

伊维菌素微球在家兔体内的药动学

皮下注射伊维菌素 (IVM )微球悬液 (5 0mg/kg及 10 0mg/kg)和害获灭 (1%伊维菌素 ,0 5mg/kg) ,RP HPLC UV法定量 ,研究了IVM在家兔体内的药物动力学。害获灭皮下注射给药 ,药 时数据符合一级吸收一室开放模型 ,主要动力学参数为 :t1/2ka=7 2 4± 2 96h ;t1/2ke=36 38± 8 6 6h ;tmax=2 1 4 6± 4 82h ;Cmax=2 2 53± 2 32ng/ml;AUC =174 9± 318ng/1.h ,其动力学参数表现比较明显的个体差异 ,且与其它动物有明显差别。微球皮下注射一周后 ,血药浓度呈较稳定状态 ,到第 4 2天 (高剂量组 )和第 32天 (低剂量组 ) ,血浆中测不出H2 B1a(低于 2 5ng/ml)。以房室模型拟合 ,微球高低剂量组均符合有吸收二室开放模型 ,主要药动学参数均表现显著的个体差异。     

阿莫西林注射用混悬液及其在猪体内的药物动力学研究

以阿莫西林为原料,注射用大豆油为溶媒,成功研究出阿莫西林注射用混悬液,并对制剂进行了稳定性研究。所有参试样品的相对含量、外观性状、粒度、分解产物等指标均无明显变化,表明该制剂对光、热稳定。选用5头健康猪进行了药物动力学研究,按15mg/kgB.W的阿莫西林剂量肌内注射,药时曲线符合一级吸收二室模型,主要动力学参数为:Tmax=0 53±0 17h,Cmax=12 33±0 47μg/ml,AUC=79 62±4 32(μg/ml)h,T1/2β=33 62±4 06h。结果表明,阿莫西林注射用混悬液在猪体内吸收缓慢,持效时间长。临床应用48h给药1次仍能维持对常见病原菌的有效血药浓度。     

动物专用头孢喹诺的研究进展

头孢喹诺是动物专用的第4代头孢菌素类抗生素,具有广泛的抗菌和强大的杀菌作用。其抗菌活性极强,对临床分离的各种革兰氏阳性菌、革兰氏阴性菌的MIC50、MIC90值均较小;其药动学特点优良,吸收快,达峰时间短,生物利用度较高,药时曲线下面积较大,表现分布容积也很大;头孢喹诺毒性低,在动物的可食用组织中残留较少,安全性较高。国外已将该药应用于猪、牛的呼吸系统感染及牛乳房炎的治疗。为指导头孢喹诺在我国兽医临床上的合理应用,现对其抗菌活性、药动学、残留及毒性、临床应用等最新资料进行综述。