Ceftazidime的犬组织浓度及药代动力学研究

PHARMACOKINETICS AND TISSUE CONCENTRATION OF CEFTAZIDIME IN DOGS

用6条健康犬进行了Ceftazidime的药代动力学研究及组织浓度测定。所有试验犬均静脉及肌肉交叉注射本品20mg/kg。药物血清浓度及组织浓度测定采用微生物杯碟法。 实验结果显示静脉及肌注后的血清药物浓度-时间曲线分别符合二室及一室开放模型。静注后即刻的平均血药浓度为167.28±15.73μg/ml,肌注0.75小时后的峰浓度为54.86±11.42μg/ml, 静注及肌注后的消除相半衰期分别为1.61小时和1.44小时,表观分布容积各为0.35L/kg和0.34L/kg。 静注及肌注Ceftazidime 20mg/kg 1小时后的组织浓度测定结果表明肾脏浓度最高,达189.03±79.38μg/ml(im)和257.04±59.19μg/ml(iv),其次是胆汁浓度。其他脏器组织浓度依下列次序减低:子宫、前列腺、肝、肺、小肠、胰腺、肌肉、心和脾。脑组织浓度最低,其值为0.31±0.lμg/ml(im)和0.77±0.09μg/ml(iv)。

The pharmacokinetics of ceftazidime were studied in dogs. Six healthy dogs were all given a single dose of 20mg/kg. Both intramuscular and intravenous administrations were used. The drug serum and tissue levels were measured by bioassay method. The serum concentration-time profiles after intramuscular injections conformed to the one-compartment open model; while those of intravenous injections monformed to the two-compartment open model. The mean peak level was 167. 28±15.73 μg/ml after intravenous injections, and was 54. 86±11.42 ,μg/ml for the intramuscular route at the post-administration time of 0.75 hour. The elimination halflives after intramuscular and intravenous injections were 1.44 and 1.61 hours,respectively.The apparetn volumes of distribution were 0.34 and 0.35 L/kg, respectively. Tissue concentrations were determined 1 hour after intravenous and intramuscular injections of 20 mg/kg. The concentration in the renal tissue was the highest, reaching 189.03 ± 79.38 μg/ml(im) and 257.04±59. 19 μg/ml(iv), and the bile concentration was the next. The concentrations in decreasing order in other tissues were uterine, prostatic, pulmonary, hepatic, small intestinal, pancreatic, muscular, cardiac and splenic. The concentrations in the brain were 0.31±0.1 μg/ml(im) and 0.77± 0.096μg/ ml(iv).