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盐酸特拉唑嗪片在健康人体的生物等效性研究

刘健1 吴丽花1 胡兴江1 吴国兰1 周惠丽1 申屠建中1

(1.浙江大学医学院附属第一医院临床药学研究中心浙江省药物临床研究与评价技术重点实验室传染病诊治国家重点实验室, 杭州 310000)
【知识点链接】生物等效性; 体位性低血压

【摘要】目的用液相色谱串联质谱法测定健康男性受试者单次空腹口服受试及参比盐酸特拉唑嗪片后的血药浓度,计算受试制剂和参比制剂的药动学参数,评价两种制剂是否生物等效。方法采用随机、开放、双周期自身交叉试验设计,18例健康男性受试者随机分成2组,单剂量口服盐酸特拉唑嗪片受试制剂和参比制剂2 mg,用LC-MS/MS测定血浆中特拉唑嗪的浓度。药动学参数用DAS 2.0软件处理获得。结果受试制剂和参比制剂tmax中位数(最小值,最大值)分别为1.00(0.25,2.00)h和0.75(0.50,4.00)h,ρmax(平均值±SD)分别为(49.72±9.86)和(61.66±18.37)ng·m L-1,AUC0-t(平均值±SD)分别为(516.35±107.33)和(616.58±118.48)ng·h·m L-1,AUC0-∞(平均值±SD)分别为(532.62±112.42)和(634.99±122.49)ng·h·m L-1,相对于参比制剂,受试制剂的相对生物利用度为(100.17±13.92)%。AUC0-t、ρmax90%置信区间分别为93.8%~105.1%和88.3%~108.4%。试验期间未发生严重不良事件。结论盐酸特拉唑嗪片受试制剂和参比制剂人体内具有生物等效性。

【关键词】 盐酸特拉唑嗪;空腹;生物等效性;液相色谱串联质谱法;药动学;

【DOI】

Bioequivalence of Terazosin Hydrochloride Tablets in Healthy Volunteers

LIU Jian1 WU Li-hua1 HU Xing-jiang1 WU Guo-lan1 ZHOU Hui-li1 SHENTU Jian-zhong1

(1.Research Center of Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China 310000)
【Knowledge Link】bioequivalence; postural hypotension

【Abstract】 OBJECTIVE To evaluate the bioequivalence of test and reference preparations of Terazosin Hydrochloride Tablets in healthy male volunteers. METHODS This is an open random and two-way crossover clinical trial involved 18 healthy male subjects. The volunteers were randomly divided into two groups. They were given a single oral dose of test and reference preparations of Terazosin Hydrochloride Tablets (2 mg for each). The plasma concentrations of terazosin were determined by LC-MS/MS. Pharmacokinetic parameters were obtained using DAS2.0 program. RESULTS The main pharmacokinetic parameters of Terazosin Hydrochloride Tablets test and reference preparations were as follows: the median (min, max) of tmax was 1.00 (0.25, 2.00) h and 0.75 (0.50, 4.00) h; ρmax was (49.72 ± 9.86) and (61.66 ± 18.37) ng·mL−1; AUC0-t was (516.35 ± 107.33) and (616.58 ± 118.48) ng·h·mL−1; AUC0-∞ was (532.62 ± 112.42) and (634.99 ± 122.49) ng·h·mL−1; the relative bioavailability of the test preparation was (100.17 ± 13.92)%; 90% CI of AUC0-t and ρmax of the test preparation was 93.8%–105.1% and 88.3%–108.4%. No serious adverse events were observed during the trials. CONCLUSION Two kinds of Terazosin Hydrochloride Tablets are bioequivalent.

【Keywords】 terazosin; fast; bioequivalence; LC-MS/MS; pharmacokinetics;

【DOI】

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This Article

ISSN:1001-2494

CN: 11-2162/R

Vol 54, No. 18, Pages 1504-1507

September 2019

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Abstract

  • 1 Materials and methods
  • 2 Results
  • 3 Discussion
  • References