头孢硫脒及头孢硫脒盐药动学及相对生物利用度探究.docVIP

头孢硫脒及头孢硫脒盐药动学及相对生物利用度探究 　 作者：张小娜 鲁澄宇 陈方 许卫铭 李忠思 吴铁 【摘要】 目的 研究家兔肌注头孢硫脒和头孢硫脒盐的药动学及相对生物利用度。方法 健康家兔12只，随机分为2组，分别肌肉注射等摩尔药物，以高效液相色谱法测定血药浓度，以Matlab程序分析计算药动学参数及相对生物利用度，判断两种制剂的生物等效性。结果 头孢硫脒和头孢硫脒盐的平均血药峰浓度(cmax)分别为(0.106±0.034)和(0.075±0.019)mmol/L，曲线下面积(AUC)分别为(6.887±1.660)和(6.293±0.707)mmol·min/L，达峰时间(Tmax)分别为(9.697±1.753)和(10.758±3.196)min，血浆清除半衰期(T1/2)分别为(39.908±10.532)和(51.547±9.383)min。两种制剂的药时曲线吻合良好，所得主要药动学参数经统计学处理，P值均gt;0.05，无显著性差异，头孢硫脒与头孢硫脒盐比较的相对生物利用度为109.4%。结论 头孢硫脒与头孢硫脒盐为生物等效制剂。 【关键词】 头孢硫脒； 头孢硫脒盐； 高效液相色谱法； 相对生物利用度 ABSTRACT Objecdive To study pharmacokinetics and relative bioavailability of cefathiamidine and cefathiamidine salt in rabbit intramuscularly. Methods 12 healthy rabbit were randomilzed divided into 2 groups and administered equal dosage of drug. The plasma concentrations of cefathiamidine and cefathiamidine salt were measured by high performance liquid chromatography (HPLC). Pharmacokinetics parameter and relative bioavailability were calculated by Matlab procedure, to judge bioequivalence of two preparations. Results Pharmacokinetics parameter of cefathiamidine and cefathiamidine salt were as follows: cmax (0.106±0.034)mmol/L and (0.075±0.019)mmol/L, AUC (6.887±1.660)mmol·min/L and (6.293±0.707) mmol·min/L, Tmax (9.697±1.753)min and (10.758±3.196)min, T1/2(ke) (39.908±10.532)min and (51.547±9.383)min. Drugtime curve of two preparations were well coincidence. No significance difference were found among pharmacokinetics parameters of two preparations. The relative bioavailability of two preparations was 109.4%. Conclusion The two preparations presented bioequivalence. KEY WORDS Cefathiamidine; Cefathiamidine salt; HPLC; Relative bioavailability 头孢硫脒(cefathiamidine)是目前唯一由我国自行研制并首先应用于临床的半合成头孢菌素衍生物，临床上主要用于敏感菌引起的呼吸道感染、创伤及外科感染、皮肤及软组织感染、尿路感染、耳鼻喉感染、心内膜炎和败血症，尤其适用于金葡菌、表葡菌、链球菌属或肠球菌等革兰阳性球菌引起的各种中、 重度感染的治疗［1，2］。本品药动学参数优于大多数第一代头孢类抗生素，血药浓度高，组织分布广，主要以原形从尿中排出［2，3］。但头孢硫脒的药动学过程及生物利用度是否优于其盐，选择头孢硫脒制剂是否优于头孢硫脒盐，目前尚未见文献报道。本研究着重比较头孢硫脒和头孢硫脒盐的药动学参数，并评价两种制剂的生物等效性，为该产品合成工艺优化，产品成本降低