注射用头孢曲松钠动物体内药代动力学和相对生物利用度研究.doc

注射用头孢曲松钠动物体内药代动力学和相对生物利用度研究 目的：对比上海新亚药业 与罗氏制药生产的两种注射用头孢曲松 钠产品（简称为新亚和罗氏芬）在SD大 鼠和食蟹猴的药代动力学性质差异。方 法：实验动物在静脉注射和肌肉注射后， 采用UPLC-MS/MS测定血浆中头孢曲松 浓度，通过Kinetica 5.1计算药代动力学 参数。结果：静脉注射后，新亚和罗氏 芬在SD大鼠体内的AUCO-t分别为483.4 ±179.5 Pg?h/ml、542.4± 166.0 U g?h/ml、在食蟹猴体内分别为1703.6土 ng?h/ml、1811.7±601.7 n g?h/ml。肌肉注射后，新亚和罗氏芬在 SD大鼠体内的AUCO-t分别为412.6 土 Pg?h/ml、451.7±147.1 ug?h/ml、 在食蟹猴体内分别为1454.9±592.9 U g?h/ml、1 367.3±772.0 ug?h/ml。相对 于罗氏芬，新亚在SD大鼠体内静脉和肌 肉注射的相对生物利用度分别为（89.1 ±98.6) %、(91.3±55.4) %、在食蟹猴 体内分别为(94.0±9.6) %、(106.4土 103.0) %。结论:两种制剂在大鼠和食 蟹猴上的药代动力学特点类似，未见显 著差异。 关键词注射用头孢曲松钠药代动 力学相对生物利用度 :R978.ll； R969.1文 献标识码：A 1006-1533(2016) 21-0070-06 Study on the pharmacokinetics of ceftriaxone sodium for injection and its relative bioavailability in SD rat and cynomolgus monkey ZANG Weijun*，GAO Yinghui， XIANG Zhixiong, ZHANG Leduo (Central Research Institute， Shanghai Pharmaceuticals Holding Co. Ltd.， Shanghai 201203，China) ABSTRACT Objective： To compare pharmacokinetic properties of two kinds of ceftriaxone sodium which were produced by Shanghai New Asia pharmaceutical and Roche pharmaceuticals (New Asia and Rocephin for short) . Methods： SD rats and cynomolgus monkeys were intravenously or intramuscularly injected with one of the two preparations， respectively. Their concentrations in plasma were determined by UPLC-MS/MS. The pharmacokinetic parameters were calculated by Kinetica 5.1. Results： The areas under the curve (AUCO-t) of New Asia and Rocephin were 483.4± 179.5 and 542.4± 166.0 u g?h/ml in SD rats and 1 703.6±564.4 and 1 811.7±601.7 u g?h/ml in cynomolgus monkeys via intravenous injection and 412.6±153.4 and 451.7土 147.1 u g?h/ml in SD rats and 1 454.9±592.9 and 1 367.3±772.0 u g?h/ml in cynomolgus monkeys via intramuscular injection， respectively. The relative bioavailability of New Asia was (89.1±98.6)% and (94.0±9.6)% in SD rat and cynomolgus monkeys via intravenous injection and (91.3 + 55.4)% and (106.4± 103.0) % in SD rat and cynomolgus monkeys via intramuscular injection， respe