前列腺素E1冻干脂微球在比格犬体内的药动学

doi:10.6040/j.issn.1671-7554.0.2015.467

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (12): 38-42.doi: 10.6040/j.issn.1671-7554.0.2015.467

前列腺素E₁冻干脂微球在比格犬体内的药动学

黄惠锋¹, 姚芳¹, 白雪^2,3

1. 浙江圣兆药物科技股份有限公司, 浙江杭州 310051;
2. 浙江中医药大学药学院, 浙江杭州 310053;
3. 山东大学国家糖工程技术研究中心, 山东济南 250100

收稿日期:2015-05-08 出版日期:2015-12-10 发布日期:2015-12-10
通讯作者: 白雪。E-mail:bxsy8011@sina.com E-mail:bxsy8011@sina.com

Pharmacokinetics of prostaglandin E₁ freeze-dried lipid microspheres in beagle dogs

HUANG Huifeng¹, YAO Fang¹, BAI Xue^2,3

1. Zhejiang Sundoc Pharmaceutical Science and Technology Co., Ltd., Hangzhou 310051, Zhejiang, China;
2. College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China;
3. National Glycoengineering Research Center, Shandong University, Jinan 250100, Shandong, China

Received:2015-05-08 Online:2015-12-10 Published:2015-12-10

摘要/Abstract

摘要： 目的考察前列腺素E₁(PGE₁)冻干脂微球在比格犬体内的药动学特征,为其临床人体用药提供参考依据。方法 24只比格犬随机分为对照组和低、中、高剂量组,每组6只,分别静脉给予参比制剂"凯时"与20、32、64μg/dog的受试制剂PGE₁冻干脂微球,于不同时间点采集血样,采用LC-MS/MS法测定比格犬体内PGE₁的血药浓度。结果比格犬静脉推注32μg/dog剂量的PGE₁冻干脂微球后,血浆中PGE₁的t_1/2为(7.5±3.7)min,t_max为(7.6±2.9)min,C_max为(105.0±40.4)ng/L,AUC_{(0~18 min)}为(933.1±359.0)ng·min/L,与参比制剂"凯时"间的差异无统计学意义(P>0.05);在低、中、高3个不同剂量下,PGE₁的AUC_{(0~18 min)}、C_max分别与剂量呈线性正相关,且性别差异无统计学意义(P> 0.05)。结论 PGE₁冻干脂微球与其市售脂微球注射液"凯时"具有相同的药动学特征,不同剂量水平不影响其在比格犬体内的药动学过程。

关键词: 前列腺素E₁, 脂微球, 药动学, LC-MS/MS

Abstract: Objective To study the pharmacokinetics of prostaglandin(PGE₁) freeze-dried lipid microspheres in beagle dogs and provide reference for its clinical usage. Methods Twenty-four beagle dogs were divided randomly into the control group, low-dose group, medium-dose group and high-dose group, six in each group. Dogs were injected intravenously with reference preparation "Kaishi" and PGE₁ freeze-dried lipid microspheres with 20, 32 and 64μg/dog, respectively. The blood samples were collected at different time points. LC-MS/MS method was used to detect the plasma concentration of PGE₁ in beagle dogs. Results After intravenous injection at a dose of 32μg/dog, t_1/2 of PGE₁ in plasma was (7.5±3.7) min, t_max was (7.6±2.9) min, C_max was (105.0±40.4)ng/L, and AUC_{(0-18 min)} was (933.1±359.0) ng·min/L, which had no difference from those of the reference formulation (P>0.05). AUC_{(0~18 min)} and C_max were positively correlated with different dose levels. Besides, the pharmacokinetic result showed there were no significant statistical difference between the sexes (P>0.05). Conclusion PGE₁ freeze-dried lipid microspheres have similar pharmacokinetic characteristics in comparison with the reference formulation, and different doses do not affect PGE₁ pharmacokinetic profile in beagle dogs.

Key words: Prostaglandin E₁, Lipid microspheres, Pharmacokinetics, LC-MS/MS

中图分类号:

R945

黄惠锋, 姚芳, 白雪. 前列腺素E₁冻干脂微球在比格犬体内的药动学[J]. 山东大学学报（医学版）, 2015, 53(12): 38-42.

HUANG Huifeng, YAO Fang, BAI Xue. Pharmacokinetics of prostaglandin E₁ freeze-dried lipid microspheres in beagle dogs[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(12): 38-42.

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前列腺素E₁冻干脂微球在比格犬体内的药动学

Pharmacokinetics of prostaglandin E₁ freeze-dried lipid microspheres in beagle dogs

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