头孢地尼在健康受试者体内生物等效性研究

发布时间：2018-03-31 08:50

  本文选题：头孢地尼　切入点：液相色谱-串联质谱法　出处：《郑州大学》2014年硕士论文

【摘要】：头孢地尼是一种新的广谱口服半合成抗菌药物,是一种口服氨基噻唑头孢菌素,对肠道革兰氏阳性和革兰氏阴性细菌均有效。对β内酰胺酶不稳定是许多头孢菌素的弱点,相对而言,头孢地尼对β内酰胺酶比较稳定,甚至对许多耐青霉素和某些头孢菌素的细菌依然敏感,头孢地尼对耳、鼻窦、咽喉和皮肤常见细菌感染有效。本研究将以广州市白云山光华制药股份有限公司生产的头孢地尼胶囊为参比制剂,考察广东省先强药业有限公司生产的头孢地尼片和分散片在健康人体中的相对生物利用度及生物等效性。目的：采用高效液相串联质谱建立测定人血浆中头孢地尼的方法学并评价头孢地尼胶囊(广州市白云山光华制药股份有限公司生产)、头孢地尼片(广东省先强药业有限公司)、头孢地尼分散片(广东省先强药业有限公司)在健康人体中的生物等效性。方法：采用随机、自身前后三交叉的实验设计,24名健康男性受试者单剂量口服100mg三种不同的头孢地尼口服制剂,采用高效液相色谱串联质谱法测定,并使用DAS2.1软件计算药代动力学参数及相对生物利用度,评价广东省先强药业有限公司生产的头孢地尼片和分散片在健康人体中的生物等效性。结果：采用高效液相色谱串联质谱法,头孢地尼的线性范围为11.50-2300.00ng.mL-1,批内、批间精密度(RSD)均小于10%。受试制剂(头孢地尼片,A药；头孢地尼分散片,B药)与参比制剂(头孢地尼胶囊,R药)的主要药动学参数分别为：Tmax分别为(3.0±0.8)、(3.2±0.9)和(3.5±0.7)h； Cmax分别为(548.96±184.58)、(607.09±236.38)和(570.18±172.37)ng·mL-1；t1/2分别为(2.0士0.3)、(1.9±0.4)和(1.9±0.3)h；梯形法算得AUCo-t分别为(2755.30±956.10)、(3037.50-±1014.40)和(2756.40±804.10)ng·h·m1-1,AUCo-∞分别为(2857.90±1011.60)、(3143.80±1038.40)和(2862.10±821.20)ng·h·m1-1。头孢地尼片(A药)和头孢地尼分散片(B药)分别以参比制剂为对照,用面积法AUCo-t估算的受试制剂的相对生物利用度分别为(104.2±37.5)%和(111.8±30.3)%。结论：建立的分析方法灵敏、快速、准确,可以用于本研究。受试制剂与参比制剂具有生物等效性。
[Abstract]:Cefdinil is a new broad-spectrum oral semi-synthetic antibiotic, an oral aminothiazole cephalosporin, which is effective against both Gram-positive and Gram-negative bacteria in the intestinal tract. Instability of 尾 -lactamases is a weakness of many cephalosporins. Cefdinil is relatively stable to 尾 -lactamases, and even sensitive to penicillin and some cephalosporins. Common bacterial infections in throat and skin are effective. The cefdini capsule produced by Guangzhou Baiyun Mountain Guanghua Pharmaceutical Co., Ltd will be used as reference preparation. To investigate the relative bioavailability and bioequivalence of cefodipine tablets and dispersible tablets produced by Xianqiang Pharmaceutical Co., Ltd., Guangdong Province. Objective: to establish a method for the determination of cefodide in human plasma by high performance liquid chromatography tandem mass spectrometry (HPLC-MS). The methodology and evaluation of cefdini capsules (Guangzhou Baiyunshan Guanghua Pharmaceutical Co., Ltd.) production of Cefdini tablets (Guangdong Province Xianqiang Pharmaceutical Co., Ltd., Cefdini dispersible tablets (Guangdong Province Xianqiang Pharmaceutical Co., Ltd. Bioequivalence in healthy humans. Methods: random, A single dose of 100mg was administered to 24 healthy male subjects and three different kinds of cefdinir were used to determine it by high performance liquid chromatography-tandem mass spectrometry (HPLC / MS). The pharmacokinetic parameters and relative bioavailability were calculated by DAS2.1 software. To evaluate the bioequivalence of cefodinil tablets and dispersible tablets produced by Xianqiang Pharmaceutical Co., Ltd in Guangdong Province in healthy volunteers. Results: the linear range of cefdinil in healthy volunteers was 11.50-2300.00ng.mL-1 by HPLC tandem mass spectrometry (HPLC / MS). RSDs were less than 10. The main pharmacokinetic parameters of cefdinir dispersible tablets) and reference preparations (cefdinil capsule R) were: Tmax: 3. 0 卤0. 8 卤0. 9 卤0. 9) and 3. 5 卤0. 7 h; Cmax: 548. 96 卤18. 58. 58. 58. 09 卤236.38) and 570. 18 卤0. 3 卤0. 3 卤0. 3 AUCo-t and 1. 9 卤0. 3; trapezoidal method, AUCo-t = 2755.30 卤956.10, 3037.50- 卤1014.40, AU56.40 卤AU56.40 卤804.10)ng h, respectively. 鈭，

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