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AUC0-t分别为483.4±179.5μg·h/ml、542.4±166.0μg·h/ml、在食蟹猴体内分别为1703.6±564.4μg·h/ml、1811.7±601.7μg·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±153.4μg·h/ml、451.7±147.1μg·h/ml、在食蟹猴体内分别为1454.9±592.9μg·h/ml、1367.3±772.0μg·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。

Study on the pharmacokinetics of ceftriaxone sodium for injection and its relative bioavailability in SD rat and cynomolgus monkey

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±166.0μg·h/ml in SD rats and 1 703.6±564.4 and 1 811.7±601.7 μg·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±772.0μg·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 signiifcant differences are not found.