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头孢他啶在家猫体内静脉注射和肌肉注射后的药代动力学

Pharmacokinetics of ceftazidime after intravenous and intramuscular administration to domestic cats.

作者信息

Albarellos G A, Ambros L A, Landoni M F

机构信息

Cátedra de Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Chorroarín 280 (1427), Buenos Aires, Argentina.

出版信息

Vet J. 2008 Nov;178(2):238-43. doi: 10.1016/j.tvjl.2007.06.026. Epub 2007 Sep 4.

Abstract

The pharmacokinetic properties of ceftazidime, a third generation cephalosporin, were investigated in five cats after single intravenous (IV) and intramuscular (IM) administration at a dose rate of 30 mg/kg. Minimum inhibitory concentrations (MICs) of ceftazidime for some Gram-negative (Escherichia coli, n=11) and Gram-positive (Staphylococcus spp., n=10) strains isolated from clinical cases were determined. An efficacy predictor, measured as the time over which the active drug exceeds the bacteria minimum inhibitory concentration (T>MIC), was calculated. Serum ceftazidime disposition was best fitted by a bi-compartmental and a mono-compartmental open model with first-order elimination after IV and IM dosing, respectively. After IV administration, distribution was rapid (t(1/2(d)) 0.04+/-0.03 h), with an area under the ceftazidime serum concentration:time curve (AUC((0-infinity))) of 173.14+/-48.69 microg h/mL and a volume of distribution (V((d(ss)))) of 0.18+/-0.04 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.19+/-0.08 L/hkg and a t(1/2) of 0.77+/-0.06 h. Peak serum concentration (C(max)), T(max), AUC((0-infinity)) and bioavailability for the IM administration were 89.42+/-12.15 microg/mL, 0.48+/-0.49 h, 192.68+/-65.28 microg h/mL and 82.47+/-14.37%, respectively. Ceftazidime MIC for E. coli ranged from 0.0625 to 32 microg/mL and for Staphylococcus spp. from 1 to 64 microg/mL. T>MIC was in the range 35-52% (IV) and 48-72% (IM) of the recommended dosing interval (8-12h) for bacteria with a MIC(90)4 microg/mL.

摘要

在五只猫身上以30mg/kg的剂量率单次静脉注射(IV)和肌肉注射(IM)后,研究了第三代头孢菌素头孢他啶的药代动力学特性。测定了从临床病例中分离出的一些革兰氏阴性菌(大肠杆菌,n = 11)和革兰氏阳性菌(葡萄球菌属,n = 10)菌株对头孢他啶的最低抑菌浓度(MIC)。计算了一个疗效预测指标,即活性药物超过细菌最低抑菌浓度的时间(T>MIC)。静脉注射和肌肉注射给药后,血清头孢他啶的处置情况分别最适合用双室和单室开放模型以及一级消除来拟合。静脉注射后,分布迅速(t(1/2(d)) 0.04±0.03小时),头孢他啶血清浓度-时间曲线下面积(AUC((0-无穷大)))为173.14±48.69μg h/mL,分布容积(V((d(稳态))))为0.18±0.04L/kg。此外,消除迅速,血浆清除率为0.19±0.08L/hkg,t(1/2)为0.77±0.06小时。肌肉注射的血清峰浓度(C(max))、T(max)、AUC((0-无穷大))和生物利用度分别为89.42±12.15μg/mL、0.48±0.49小时、192.68±65.28μg h/mL和82.47±14.37%。头孢他啶对大肠杆菌的MIC范围为0.0625至32μg/mL,对葡萄球菌属为1至64μg/mL。对于MIC(90)为4μg/mL的细菌,T>MIC在推荐给药间隔(8 - 12小时)的35 - 52%(静脉注射)和48 - 72%(肌肉注射)范围内。

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