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(1)
摘 要 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AUC0-t分别为483.4±179.5 μg·h/ml、542.4±166.0 μg·h/ml、在食蟹猴体内分别为1 703.6±564.4 μg·h/ml、1 811.7±601.7 μg·h/ml。肌肉注射后，新亚和罗氏芬在SD大鼠体内的AUC0-t分别为412.6±153.4 μg·h/ml、451.7±147.1 μg·h/ml、在食蟹猴体内分别为1 454.9±592.9 μg·h/ml、1 367.3±772.0 μg·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±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
中图分类号：R978.11； R969.1 文献标识码：A 文章编号：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 (AUC0-t) of New Asia and Rocephin were 483.4±179.5 and 542.4±166.0 μg·h/ml in SD rats and 1 703.6±564.4 and 1 811.7±601.7μg·h/ml in cynomolgus monkeys via intravenous injection and 412.6±153.4 and 451.7±147.1 μg·h/ml in SD rats and 1 454.9±592.9 and 1 367.3±772.0 μg·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， respectively. Conclusion： The pharmacokinetic properties of both preparations in SD rats and cynomolgus monkeys are similar and the significant differences are not found.
KEY WORDS ceftriaxone sodium for injection； pharmacokinetic； relative bioavailability
注射用头孢曲松钠属于头孢第三代广谱抗生素，具有广谱、高效、长效及不良反应少等特点，临床常用于控制格兰阴性菌引起的感染[1]。目前国内外有众多企业生产该产品，上海新亚药业为其中之一。本文研发了一种应用UPLC-MS/MS检测头孢曲松钠的方法，它具有高灵敏度、高选择性的特点。运用此方法研究了上海新亚药业产品(简称新亚)和原研企业罗氏制药产品(罗氏芬)在大鼠和食蟹猴体内的药代动力学特性，并进行等效性分析[2-3]，以期为新亚产品的临床应用提供依据。
1 材料和方法, 百拇医药(臧卫军 高颖慧 向志雄 张乐多)
关键词 注射用头孢曲松钠 药代动力学 相对生物利用度
中图分类号：R978.11； R969.1 文献标识码：A 文章编号：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 (AUC0-t) of New Asia and Rocephin were 483.4±179.5 and 542.4±166.0 μg·h/ml in SD rats and 1 703.6±564.4 and 1 811.7±601.7μg·h/ml in cynomolgus monkeys via intravenous injection and 412.6±153.4 and 451.7±147.1 μg·h/ml in SD rats and 1 454.9±592.9 and 1 367.3±772.0 μg·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， respectively. Conclusion： The pharmacokinetic properties of both preparations in SD rats and cynomolgus monkeys are similar and the significant differences are not found.
KEY WORDS ceftriaxone sodium for injection； pharmacokinetic； relative bioavailability
注射用头孢曲松钠属于头孢第三代广谱抗生素，具有广谱、高效、长效及不良反应少等特点，临床常用于控制格兰阴性菌引起的感染[1]。目前国内外有众多企业生产该产品，上海新亚药业为其中之一。本文研发了一种应用UPLC-MS/MS检测头孢曲松钠的方法，它具有高灵敏度、高选择性的特点。运用此方法研究了上海新亚药业产品(简称新亚)和原研企业罗氏制药产品(罗氏芬)在大鼠和食蟹猴体内的药代动力学特性，并进行等效性分析[2-3]，以期为新亚产品的临床应用提供依据。
1 材料和方法, 百拇医药(臧卫军 高颖慧 向志雄 张乐多)