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头孢羟氨苄在马体内的药代动力学及体外抗菌活性

Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity.

作者信息

Wilson W D, Baggot J D, Adamson P J, Hirsh D C, Hietala S K

出版信息

J Vet Pharmacol Ther. 1985 Sep;8(3):246-53. doi: 10.1111/j.1365-2885.1985.tb00953.x.

Abstract

Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24-h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one-compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 +/- 15.0 micrograms/ml; half-life = 46 +/- 20 min; apparent volume of distribution = 462 +/- 191 ml/kg; and body clearance = 7.0 +/- 0.6 ml/min.kg. In a subsequent study, a suspension of cefadroxil monohydrate was administered intragastrically (25 mg/kg) to the same six horses. Plasma concentrations of the drug peaked at 1-2 h but, in general, absorption was both poor and inconsistent. The data were unsuitable for determination of cefadroxil bioavailability from this oral dosage form. Ninety-nine isolates of eleven bacterial species obtained from clinically ill horses were tested for susceptibility to cefadroxil. All strains of Streptococcus equi, Streptococcus zooepidemicus, coagulase-positive staphylococci, Corynebacterium pseudotuberculosis and five out of six strains of Actinobacillus suis were highly susceptible to the drug (MIC less than 4 micrograms/ml). Escherichia coli, Klebsiella pneumoniae and Salmonella sp. showed intermediate susceptibility (MIC 4-16 micrograms/ml), while all isolates of Corynebacterium (Rhodococcus) equi, Enterobacter cloacae and Pseudomonas aeruginosa proved to be highly resistant to cefadroxil (MIC greater than 128 micrograms/ml).

摘要

对6匹健康成年母马静脉注射单剂量头孢羟氨苄钠(25毫克/千克)。在24小时内采集血样,采用微生物学测定法测定头孢羟氨苄浓度。该药物的药代动力学行为用单室开放模型进行了恰当描述。主要药代动力学参数值如下:外推初始血药浓度 = 59.2±15.0微克/毫升;半衰期 = 46±20分钟;表观分布容积 = 462±191毫升/千克;机体清除率 = 7.0±0.6毫升/分钟·千克。在随后的一项研究中,对同一6匹马灌胃给予一水合头孢羟氨苄混悬液(25毫克/千克)。药物血药浓度在1 - 2小时达到峰值,但总体而言,吸收较差且不稳定。这些数据不适合用于测定该口服剂型的头孢羟氨苄生物利用度。对从临床患病马匹分离出的11种细菌的99株菌株进行了头孢羟氨苄敏感性测试。所有马链球菌、兽疫链球菌、凝固酶阳性葡萄球菌、伪结核棒状杆菌菌株以及6株猪放线杆菌中的5株对该药物高度敏感(最低抑菌浓度小于4微克/毫升)。大肠杆菌、肺炎克雷伯菌和沙门氏菌属表现出中度敏感性(最低抑菌浓度4 - 16微克/毫升),而所有马红球菌、阴沟肠杆菌和铜绿假单胞菌分离株对头孢羟氨苄高度耐药(最低抑菌浓度大于128微克/毫升)。

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