阿米卡星脂质体在家兔体内的药动学研究

为研究阿米卡星脂质体在家兔体内的代谢动力学,给家兔一次静注阿米卡星脂质体(12.5 mg/kg),在 24 h内不同时间点取血样测定血药浓度.结果表明:药-时曲线符合一室开放模型,其主要药代动力学参数分别为:生物半衰期(t1/2β)7.39 h,表观分布容积(V)38.43 mL,药时曲线下面积(AUC)7 487.34 h·μg/mL,清除率(CLB)3.80mL/h.     

Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose

Reasons for performing study: No studies have determined the pharmacokinetics of low‐dose amikacin in the mature horse. Objectives: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n = 6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n = 6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean ± s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time zero 144 ± 21.8 µg/ml; extrapolated plasma concentration for the elimination phase 67.8 ± 7.44 µg/ml, area under the curve 139 ± 34.0 µg*h/ml, elimination half‐life 1.34 ± 0.408 h, total body clearance 1.25 ± 0.281 ml/min/kg bwt; and mean residence time (MRT) 1.81 ± 0.561 h. At 24 h, the plasma concentration of amikacin for all horses was below the minimum detectable concentration for the assay. Selected parameters in synovial and peritoneal fluid were maximum concentration (C_max) 19.7 ± 7.14 µg/ml and 21.4 ± 4.39 µg/ml and time to maximum concentration 65 ± 12.2 min and 115 ± 12.2 min, respectively. Amikacin in the interstitial fluid reached a mean peak concentration of 12.7 ± 5.34 µg/ml and after 24 h the mean concentration was 3.31 ± 1.69 µg/ml. Based on a minimal inhibitory concentration (MIC) of 4 µg/ml, the mean C_max : MIC ratio was 16.9 ± 1.80 in plasma, 4.95 ± 1.78 in synovial fluid, 5.36 ± 1.10 in peritoneal fluid and 3.18 ± 1.33 in interstitial fluid. Conclusions: Amikacin dosed at 10 mg/kg bwt i.v. once a day in mature horses is anticipated to be effective for treatment of infection caused by most Gram‐negative bacteria. Potential relevance: Low dose amikacin (10 mg/kg bwt) administered once a day in mature horses may be efficacious against susceptible microorganisms.     

Amikacin-induced Fin Reduction is Mediated by Autophagy

Despite its medical use, little is known about the mechanisms underlying amikacin-induced embryotoxicity, including fin reduction, in zebrafish. In this study, we examined the expression of well-known autophagy markers mTOR (target of rapamycin), atg10 (autophagy-related gene), atg12 and LC3 (mammalian homolog of Atg8) in amikacin-treated zebrafish embryos. Our results indicated that the mRNA expression level of atg12 in the amikacin-treated group was significantly increased by 1.5-fold (p<0.05) compared with the corresponding mock control group, while the expression levels of atg10 and mTOR were significantly decreased by 0.74-fold (p<0.05) and 0.58-fold (p<0.05), respectively. Western blot analysis revealed that LC3 protein expression was induced by amikacin. Taken together, these data suggest that amikacin-induced fin reduction is mediated by fin cell autophagy.     

阿米卡星脂质体的研制及体外抑菌试验

为研究阿米卡星脂质体的体外抑菌效果 ,采用逆相蒸发法制备阿米卡星脂质体 ,利用Hantzsh反应测定其包封率 ,并比较阿米卡星脂质体和游离阿米卡星对大肠杆菌、链球菌、巴氏杆菌、金葡菌的最小抑菌浓度和最小杀菌浓度。结果表明 :阿米卡星脂质体的包封率较高 ,达到6 1 .8%,阿米卡星脂质体对大肠杆菌、链球菌、巴氏杆菌、金葡菌的最低抑菌浓度分别约为游离阿米卡星的 1/3.5,1/7,1 /2 ,1/2 ,最低杀菌浓度分别约为游离阿米卡星的 1/4,1 /4,1/1 .8,1 /4,证明阿米卡星脂质体的体外抗菌作用明显优于游离阿米卡星     

The disposition kinetics,urinary excretion and dosage regimen of amikacin in cross-bred bovine calves

The disposition kinetics, urinary excretion and dosage regimen of amikacin after a single intravenous administration of 10 mg/kg was investigated in six cross-bred bovine calves. At 1 min, the concentration of amikacin in the plasma was 116.9±3.16 µg/ml and the minimum therapeutic concentration was maintained for 8 h. The elimination half-life and volume of distribution were 3.09±0.27 h and 0.4±0.03 L/kg, respectively. The total body clearance (Cl_B) and T/P ratio were 0.09±0.002 L/kg/h and 4.98±0.41, respectively. Approximately 50% of the total dose of amikacin was recovered in the urine within 24 h after administration. Amikacin in concentrations ranging from 5 to 150 µg/ml bound to plasma proteins to the extent of 6.32%±0.42%. A satisfactory intravenous dosage regimen of amikacin in bovine calves would be 13 mg/kg followed by 12 mg/kg at 12 h intervals.     

Pharmacokinetics of Amikacin in Lactating Sheep

The pharmacokinetics of amikacin (AMK) were investigated after intravenous (i.v.) and intramuscular (i.m.) administration of 7.5 mg/kg bw in 6 healthy lactating sheep. After i.v. AMK injection (as a bolus), the elimination half-life (t1/2beta), the volume of distribution (Vd,area), the total body clearance (ClB) and the area under the concentration-time curve (AUC) were 1.64 +/- 0.06 h, 0.19 +/- 0.02 L/kg, 1.36 +/- 0.1 ml/min per kg and 94.09 +/- 6.95 (microg.h)/ml, respectively. The maximum milk concentration of AMK (Cmax), the area under the milk concentration-time curve (AUCmilk) and the ratio AUCmilk/AUCserum were 1.18 +/- 0.22 microg/ml, 22.45 +/- 3.21 (micro.h)/ml and 0.24 +/- 0.02, respectively. After i.m. administration of AMK the t1/2beta, Cmax, time of Cmax (tmax) and absolute bioavailability (Fabs) were 1.29 +/- 0.1 h, 16.97 +/- 1.54 microg/ml, 1.0 +/- 0 h and 64.88% +/- 6.16%, respectively. The Cmax, AUCmilk and the ratio AUCmilk/AUCserum were 0.33 microg/ml, 1.67 (microg.h)/ml and 0.036, respectively.     

阿米卡星对赤藓红的褪色反应及其分析应用

在酸性介质中,阿米卡星（AMK）与赤藓红（TIF）反应生成离子缔合物,导致赤藓红褪色．其最大褪色波长位于527nm,AMK在0．064-2．500μg／mL浓度范围内遵从比尔定律,表观摩尔吸光系数（ε）为1．46×10^5 L·mol^-1·cm^-1,考察了褪色反应的光谱特征、适宜的反应条件和共存物质的影响．方法具有良好的选择性,用于人体血清及尿样中阿米卡星的测定,结果满意．     

硫酸阿米卡星脂质体对小鼠的毒性研究

按750mg／kg体重给小鼠腹腔注射硫酸阿米卡星脂质体,7d后小鼠仍健活;再将80只小鼠随机分为4组,即140、70、35mg／kg和阴性对照组,连续20d腹腔注射硫酸阿米卡星脂质体后,进行血液学、血清生化学和组织病理学检查,结果与对照组无显著性差异。表明硫酸阿米卡星被制成脂质体制剂后,毒副作用大大降低,对动物无毒副作用。     

阿米卡星脂质体对猪肺疫的疗效试验

为研究阿米卡星脂质体的临床疗效,对10例被诊断为患猪肺疫（猪巴氏杆菌病）的仔猪进行了疗效试验。将患猪随机分为3组,空白对照组肌肉注射生理盐水;药物对照组肌肉注射阿米卡星,剂量为7．5mg／kg,每天用药2次,连用5d;试验药物组肌注阿米卡星脂质体,剂量为5．0mg／kg,每天用药1次,连用3d。结果表明,阿米卡星脂质体组治愈率和有效率分别为70．0％和76．0％,疗效显著高于药物对照组（P〈0．01）。