国产注射用甲磺酸帕珠沙星在健康人体的药代动力学研究

doi:10.5246/jcps.2019.01.005

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (1): 40-48.DOI: 10.5246/jcps.2019.01.005

国产注射用甲磺酸帕珠沙星在健康人体的药代动力学研究

欧阳文鹃¹, 张亚兰¹, 徐平声¹, 戴智勇², 马虹英², 秦群^1*

1. 中南大学湘雅医院国家药物临床试验中心, 湖南长沙 410008
2. 中南大学湘雅医院药学部, 湖南长沙 410008

收稿日期:2018-07-18 修回日期:2018-09-20 出版日期:2019-01-27 发布日期:2018-10-11
通讯作者: Tel.: +86-0731-84327918, E-mail: qinqun8087@hotmail.com

Pharmacokinetics of Pazufloxacin Mesilate Sodium Chloride in healthy Chinese volunteers after intravenous injection

Wenjuan OuYang¹, Yalan Zhang¹, Pingsheng Xu¹, Zhiyong Dai², Hongying Ma², Qun Qin^1*

1. National Institution of Drug Clinical Trial, XiangYa Hospital, Central South University, Hunan, 410008, China
2. Department of Pharmacy, XiangYa Hospital, Central South University, Hunan, 410008, China

Received:2018-07-18 Revised:2018-09-20 Online:2019-01-27 Published:2018-10-11
Contact: Tel.: +86-0731-84327918, E-mail: qinqun8087@hotmail.com

摘要/Abstract

摘要：

评价多个剂量的氟喹诺酮类抗菌药物—甲磺酸帕珠沙星在健康人体单次静脉滴注后的药代动力学参数及其在健康人体中的代谢特点。本文采用随机、开放、平行的试验设计, 根据入排标准筛选30名健康受试者, 随机分成3组, 每组10人, 分别静脉滴注低(150 mg)、中(300 mg)、高(600 mg)三个浓度的甲磺酸甲磺酸帕珠沙星, 30分钟内完成。采集不同时间点血液样本, 收集0–24小时尿液。采用反向高效液相色谱法(RP-HPLC)测定血药浓度及尿药浓度, 用DAS 1.0软件计算药代动力学参数。结果发现, 低、中、高三个剂量组药代动力学参数均符合二室模型。三个剂量组中曲线下面积(AUC_0→∞)分别为: 3.24±1.2, 5.89±1.51和13.32±2.35 mg·h·mL^–1; 峰浓度(C_max)分别为2.37±0.89, 4.27±0.74以及10.74±4.06 mg·mL^–1; 此外, 达峰时间(T_max)分别为0.48±0.08, 0.50±0.00 and 0.53±0.08 h。低、中、高三个剂量组清除率分别为(8.29±4.06 L/h), (10.96±4.42 L/h), (9.14±1.72 L/h)。分别将AUC_0→∞、C_max与剂量进行相关性分析发现, 甲磺酸帕珠沙星药物浓度与给药剂量呈线性关系。数据表明, 低、中、高三个剂量组均符合药代动力学二室模型。在150–600 mg剂量范围内, 甲磺酸帕珠沙星药物浓度与给药剂量呈线性关系。三个剂量组甲磺酸帕珠沙星药物代谢率均在90%以上, 其代谢特点与国外文献报道基本一致。

关键词: 甲磺酸甲磺酸帕珠沙星, 反向高效液相色谱, RP-HPLC, 药代动力学

Abstract:

In the present study, we aimed to investigate the pharmacokinetics and dosage proportionality for a single, intravenous utilization of Pazufloxacin Mesilate Sodium Chloride, an injectable synthetic fluoroquinolone antibacterial agent, in healthy Chinesevolunteers.In this open-labeled, three-dosage parallel study, subjects were randomized to receive a single dose of Pazufloxacin Mesilate at 150, 300 or 600 mg (n = 10, 10 and 10, respectively) administered as a 30-min intravenous infusion. Blood and urine samples were serially collected from 0 to 24 h after drug administration. Moreover, the sample’s drug concentrations were analyzed via validated RP-HPLC method.Subjects receiving a single dose of Pazufloxacin Mesilate 150, 300 or 600 mg were in accordance with the two compartment model. The C_max for each dosage group was 2.37±0.89, 4.27±0.74 and 10.74±4.06 mg·mL^–¹, respectively; and the AUC_0→∞was 3.24±1.2, 5.89±1.51 and 13.32±2.35 mg·h·mL^–¹, respectively. In addition, T_max for groups treated with 150, 300 and 600 mg was 0.48±0.08, 0.50±0.00 and 0.53±0.08 h, respectively. The correlation analysis for AUC_0→∞, C_max and dosage suggested that pazufolxacin mesilate displayed dose proportion at the dose ranging from 150 to 600 mg. The data suggested that all three different dosage regimens fit with the two compartment model. Meanwhile, it presented a linear correlation between AUC_0→∞, C_max and dosage over the range of 150–600 mg.

Key words: Pazufloxacin Mesilate, Accumulative urine excretion rate, RP-HPLC, Pharmacokinetics

中图分类号:

R969.1

Supporting:

欧阳文鹃, 张亚兰, 徐平声, 戴智勇, 马虹英, 秦群. 国产注射用甲磺酸帕珠沙星在健康人体的药代动力学研究[J]. 中国药学(英文版), 2019, 28(1): 40-48.

Wenjuan OuYang, Yalan Zhang, Pingsheng Xu, Zhiyong Dai, Hongying Ma, Qun Qin. Pharmacokinetics of Pazufloxacin Mesilate Sodium Chloride in healthy Chinese volunteers after intravenous injection[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(1): 40-48.

参考文献

[1] Misuyama, J.; Miyazaki, S.; Ishii, Y. Antibacterial activeity of a new injecttable quinolone pazufloxacin in vitro and in vivo. Jpn. J. Chemother. 1999, 47, 1-15.

[2] Mitsuyama, J.; Takahata, M.; Yamashiro, Y. Antibacterial activity of a new injectable quinolone, Pazufloxacin Mesilate, in vitro and in vivo. Jpn. J. Chemother. 1999, 47, 37-64.

[3] Nishino, T.; Ikeda, Y.; Otsuki, M. In vitro and in vivo antibacterial activity of pazufloxacin mesilate, a new parenteral fluoroquinolone. Jpn. J. Chemother. 1999, 47, 25-36.

[4] Mikamo, H.; Sato, Y.; Hayasaki, Y.; Kawazoe, K.; Tamaya, T. In vitro activities of pazufloxacin, an injectable new quinolone, against bacteria causing infections in obstertric and gynecological patients. Jpn. J. Chemother. 1999, 47, 16-38.

[5] Minami, S.; Hattori, R.; Matsuda, A. Pharmacological properties and expected clinical role of an injectable new quinolone antibiotic, pazufloxacin mesilate. Nihon Yakurigaku Zasshi. 2003, 122, 161-178.

[6] Fukuda, H.; Morita, Y.; Shiotani, N. Effect of pazufloxacin mesilate, a new quinolone antibacterial agent, for intravenous use on QT interval. Jpn. J. Antibiot. 2004, 404-412.

[7] Lee, J.; Seong, S.J.; Lim, M.S. Single-dose pharmacokinetics and dose proportionality of intravenous pazufloxacin mesilate in healthy Korean volunteers. Expert Opin. Drug Metab. Toxicol. 2012, 8, 921-928.

[8] Li, Y.; Liu, L.; Li, K.X. Parmacokinetics of pazufloxacin mesilate sodium chloride injection in Chinese healthy volunteers. Chin. J. Clin. Pharmacol. 2005, 21, 29-32.

[9] Johnson, A.P. A review of pazufloxacin including pharmacokinetic data. Pazufloxacin Toyama Chemical Co. Curr. Opin. Investig Drugs. 2000, 1, 52-57.

[10] Wang, X.G.; Miao, J.; Liang, D.R.; Yu, Q.; Liang, M.Z.; Zhang, S.H. The Clinical Pharmacokinetic/Pharmacodynamic Study of Mesilate Sodium Chloride Injection. J. Sichuan Univ.(Med. Sci. Ed). 2009, 40, 689-693.

[11] Wang, J.; Xiao, Y.H.; Zhan, W.; Lv, Y.; Kang, Z.S.; Zhang, M.; Liu, Y.; Xia, Y.H.; Li, T.Y. Pharmacokinetics of multiple-dose pazufloxacin mesilate sodium chloride injection in Chinese healthy volunteers. Chin. J. Clin. Pharmacol. 2007, 23, 24-27.

[12] Shimizu, A.; Miyoshi, M.; Sugie, M. Possible involvement of P-glycoprotein in renal excretion of pazufloxacin in rats. Eur. J. Pharmacol. 2004, 501, 151-159.

[13] Alvarez, A.I.; Pérez, M.; Prieto, J.G. Fluoroquinolone efflux mediated by ABC transporters. J. Pharm. Sci. 2008, 97, 3483-3493.

[14] Hagenbuch, B. Drug uptake systems in liver and kidney: a historic perspective. Clin. Pharmacol. Ther. 2010, 87, 39-47.

[1]	杨雁芳, 韦玮, 张雷, 徐嵬, 杨秀伟. UPLC-MS/MS法测定都梁丸中37个成分在大鼠体内的药代动力学[J]. 中国药学(英文版), 2023, 32(7): 560-573.
[2]	李晓娇, 栾树鑫, 张洪, 万洪泉, 陈红, 刘成娇, 刘畅, 丁艳华. 单剂量长效利培酮注射液在中国精神分裂症患者体内的药代动力学、药效学和安全性研究[J]. 中国药学(英文版), 2021, 30(3): 206-217.
[3]	周艳, 宋恒文, 邵志超, 尹博民, 付西美, 谢典佑, 韦利军. 一种新的细胞周期蛋白依赖性激酶(CDK)9抑制剂QHRD107对急性髓系白血病的临床前疗效[J]. 中国药学(英文版), 2021, 30(2): 146-156.
[4]	杨秀伟, 张友波, 徐嵬. 静脉和灌胃给予大鼠茴香酸对羟基苯乙酯的RP-HPLC法测定和药代动力学研究[J]. 中国药学(英文版), 2020, 29(11): 804-812.
[5]	杨辉, 胡小鹏, 杨晓勇, 刘航, 任亮, 王玮, 刘丽宏, 张小东. 肾移植术后糖皮质激素和他克莫司的药代动力学相互作用[J]. 中国药学(英文版), 2019, 28(4): 257-263.
[6]	刘鑫, 张波, 梅丹, 黄凯. HPLC-MS/MS法测定大鼠血浆中异绿原酸B浓度及其在药代动力学研究中的应用[J]. 中国药学(英文版), 2019, 28(3): 167-173.
[7]	张玲玲, 张慧文, 武世奎, 刘宏, 李静媛, 董馨, 夏慧敏, 王焕芸. UPLC-Q-Exactive-MS 同时测定三臣丸中六种活性成分的药代动力学研究[J]. 中国药学(英文版), 2019, 28(11): 812-824.
[8]	常馨予, 郭桂明, 范峥, 王宏蕾, 刘洋, 韩丽娟. UPLC-MS/MS法测定黄芪桂枝五物汤在大鼠血浆中两种活性成分及药代动力学研究[J]. 中国药学(英文版), 2018, 27(4): 263-272.
[9]	Agha Zeeshan Mirza. HPLC-UV method for simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone in formulations and in human serum[J]. 中国药学(英文版), 2018, 27(4): 273-280.
[10]	姜华, 杨景明, 曹玲, 贾桂枝, 戴红良, 孟祥才. 高温胁迫对防风药材药代动力学和药效的影响[J]. 中国药学(英文版), 2018, 27(2): 109-115.
[11]	代华灵, 高伟祺, 张国顺, 王锐利, 张淑秋. 青蒿素脂质纳米粒的制备及药动学评价[J]. 中国药学(英文版), 2017, 26(3): 180-186.
[12]	崔婷, 周岐新, 张丹, 蒋心惠. 五种大黄蒽醌类化合物在家兔和大鼠体内的分布和药代动力学[J]. 中国药学(英文版), 2017, 26(2): 115-123.
[13]	朱刚直, 易勤, 范志宏, 马岳慧, 王丹丹, 王磊, 程泽能. LC-MS/MS法测定大鼠血浆中PAC-1的新型抗癌衍生物的浓度及其药物动力学研究[J]. 中国药学(英文版), 2017, 26(11): 811-818.
[14]	文周, 冀闪, 谢非凡, 胡高云, 程泽能. 高效液相色谱法测定大鼠血浆中新型抗纤维化药物美氟尼酮的浓度及其药物动力学研究[J]. 中国药学(英文版), 2017, 26(1): 45-52.
[15]	谢湘, 周瑞, 周培根, 余鹏, 高峰. LC-MS-MS法测定人血浆中的替诺福韦[J]. 中国药学(英文版), 2016, 25(9): 676-682.

国产注射用甲磺酸帕珠沙星在健康人体的药代动力学研究

Pharmacokinetics of Pazufloxacin Mesilate Sodium Chloride in healthy Chinese volunteers after intravenous injection

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价