盐酸达拉他韦片在中国健康受试者中的生物等效性研究

doi:10.12092/j.issn.1009-2501.2026.01.006

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (1): 55-62.doi: 10.12092/j.issn.1009-2501.2026.01.006

• 临床药理学 • 上一篇

盐酸达拉他韦片在中国健康受试者中的生物等效性研究

谢晶¹^,²(), 王小妮², 闵捷³, 刘敏³, 朱旭², 胡旺², 卢畅¹, 张冉¹, 周焕²^,*(), 宫建¹^,*()

1. 沈阳药科大学生命科学与生物制药学院药物流行病与临床药物评价课题组，沈阳 110016，辽宁
2. 蚌埠医科大学第一附属医院临床试验研究中心，蚌埠 233000，安徽
3. 南京圣和药业股份有限公司，南京 210000，江苏

收稿日期:2024-06-11 修回日期:2024-09-24 出版日期:2026-01-26 发布日期:2026-02-13
通讯作者: 周焕,宫建 E-mail:2606283391@qq.com;zhouhuanbest@vip.163.com;fanxing1230@163.com
作者简介:谢晶，女，硕士，研究方向：临床药学。E-mail：2606283391@qq.com
基金资助:
中国医药教育协会临床用药卫生技术评估专项课题（2023WSJSPGZXKT-27）

Study on bioequivalence evaluation of daclatasvir hydrochloride tablets in healthy Chinese subjects

Jing XIE¹^,²(), Xiaoni WANG², Jie MIN³, Min LIU³, Xu ZHU², Wang HU², Chang LU¹, Ran ZHANG¹, Huan ZHOU²^,*(), Jian GONG¹^,*()

1. Research Group of Jian Gong on Pharmacoepidemiology and Clinical Drug Evaluation, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
2. Clinical Trial Research Center, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, Anhui, China
3. Nanjing Sanhome Pharmaceutical Co., Ltd, Nanjing 210000, Jiangsu, China

Received:2024-06-11 Revised:2024-09-24 Online:2026-01-26 Published:2026-02-13
Contact: Huan ZHOU,Jian GONG E-mail:2606283391@qq.com;zhouhuanbest@vip.163.com;fanxing1230@163.com

摘要/Abstract

摘要：

目的: 评估受试制剂盐酸达拉他韦片与参比制剂盐酸达拉他韦片（百立泽^TM）在中国健康受试者中的生物等效性和安全性。方法: 采用单次给药、随机、开放、两周期、双交叉试验设计，入组60例健康受试者，空腹组和餐后组各30例。受试者随机分成两组，第一周期单次口服1片（60 mg）受试制剂或参比制剂，第8天交叉服药。结果: 空腹组盐酸达拉他韦片受试制剂和参比制剂的主要药代动力学参数：C_max分别为（1 102.690±311.345）和（1 174.800±361.642） ng/mL；AUC_0-t分别为（13 517.051±3 576.349）和（13 503.448±4 022.914） h·ng·mL^?1；AUC_0-∞分别为（13 672.052±3 626.297）和（13 669.602±4 059.563）h·ng·mL^?1。餐后组盐酸达拉他韦片受试制剂和参比制剂的主要药代动力学参数：C_max分别为（791.733±230.334）和（872.000±303.921）ng/mL；AUC_0-t分别为（10 974.708±3 213.564）和（11 217.253±4 060.319）h·ng·mL^?1；AUC_0-∞分别为（11 140.018±3 261.934）和（11 396.162±4 143.077）h·ng·mL^?1。空腹及餐后条件下，受试者口服盐酸达拉他韦片受试制剂与参比制剂60 mg后血浆中的达拉他韦的主要药代动力学参数（C_max、AUC_0-t和AUC_0-∞）的几何均值比的90%置信区间均在80.00%～125.00%范围内。两组均无严重不良事件。结论: 在空腹或餐后状态下，盐酸达拉他韦片受试制剂与参比制剂具有生物等效性，且安全性良好。

关键词: 盐酸达拉他韦片, 药物动力学, 生物等效性

Abstract:

AIM: To evaluate the bioequivalence and safety of the test formulation of daclatasvir hydrochloride tablets and the reference formulation of daclatasvir hydrochloride tablets (DAKLINZA^TM) in healthy Chinese subjects. METHODS: A single-dose, randomized, open-label, two-cycle, double-crossover design was used, and 60 healthy subjects were enrolled. The subjects were randomly divided into two groups, with 30 subjects in the fasting group and 30 subjects in the fed group. In the first cycle, one tablet (60 mg) of the test or reference formulation was taken orally as a single dose, and cross-administration was conducted on the 8th day. RESULTS: The main pharmacokinetic parameters of the test and reference formulations of daclatasvir hydrochloride tablets in the fasting group were as follows: C_max (1 102.690±311.345) and (1 174.800±361.642) ng/mL; AUC_0-t (13 517.051±3 576.349) and (13 503.448±4 022.914) h·ng·mL^?1; AUC_0-∞ (13 672.052±3 626.297) and (13 669.602±4 059.563) h·ng·mL^?1. The main pharmacokinetic parameters of the test and reference formulations of daclatasvir hydrochloride tablets in the fed group were as follows: C_max (791.733±230.334) and (872.000±303.921) ng/mL; AUC_0-t (10 974.708±3 213.564) and (11 217.253±4 060.319) h·ng·mL^?1; AUC_0-∞ (11 140.018±3 261.934) and (11 396.162±4 143.077) h·ng·mL^?1. The 90% confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters (C_max, AUC_0-t and AUC_0-∞) of daclatasvir in plasma after oral administration of 60 mg of the test and reference formulations of daclatasvir hydrochloride tablets under fasting and fed conditions fell within the 80.00%–125.00% equivalence interval. There were no serious adverse events in both groups. CONCLUSION: The test and reference formulations of daclatasvir hydrochloride tablets were determined to be bioequivalent and safe under fasting or fed conditions.

Key words: daclatasvir hydrochloride tablets, pharmacokinetics, bioequivalence

中图分类号:

R969.1

谢晶, 王小妮, 闵捷, 刘敏, 朱旭, 胡旺, 卢畅, 张冉, 周焕, 宫建. 盐酸达拉他韦片在中国健康受试者中的生物等效性研究[J]. 中国临床药理学与治疗学, 2026, 31(1): 55-62.

Jing XIE, Xiaoni WANG, Jie MIN, Min LIU, Xu ZHU, Wang HU, Chang LU, Ran ZHANG, Huan ZHOU, Jian GONG. Study on bioequivalence evaluation of daclatasvir hydrochloride tablets in healthy Chinese subjects[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(1): 55-62.

图/表 7

参考文献 20

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Items	Fasting	Fed
Gender (man/female)	25/5	25/5
Age (years)	32.07 ± 12.14	29.03 ± 9.09
Height (cm)	168.98 ± 8.65	169.52 ± 8.35
Body weight (kg)	64.90 ± 9.99	64.85 ± 8.85
BMI (kg/m²)	22.62 ± 1.92	22.52 ± 2.00
Rance (Han Chinese/Non-Han Chinese)	29/1	30/0

Items	Fasting	Fed
Gender (man/female)	25/5	25/5
Age (years)	32.07 ± 12.14	29.03 ± 9.09
Height (cm)	168.98 ± 8.65	169.52 ± 8.35
Body weight (kg)	64.90 ± 9.99	64.85 ± 8.85
BMI (kg/m²)	22.62 ± 1.92	22.52 ± 2.00
Rance (Han Chinese/Non-Han Chinese)	29/1	30/0

Conentration (ng/mL)	Intra-day ($ \overline{x} $±s, n=6, ng/mL)	CV (%)	RE (%)	Inter-day ($ \overline{x} $±s, n=18, ng/mL)	CV (%)	RE (%)	Relative recovery (%)
3.00	2.96±0.0540	1.8	?1.3	2.99±0.0849	2.8	?0.3	/
8.00	8.17±0.146	1.8	2.1	8.07±0.236	2.9	0.9	89.8
150	157±3.25	2.1	4.7	156±5.61	3.6	4.0	/
800	829±15.7	1.9	3.6	807±26.8	3.3	0.9	93.1
1500	1480±9.83	0.7	?1.3	1440±58.3	4.0	?4.0	89.5

Conentration (ng/mL)	Intra-day ($ \overline{x} $±s, n=6, ng/mL)	CV (%)	RE (%)	Inter-day ($ \overline{x} $±s, n=18, ng/mL)	CV (%)	RE (%)	Relative recovery (%)
3.00	2.96±0.0540	1.8	?1.3	2.99±0.0849	2.8	?0.3	/
8.00	8.17±0.146	1.8	2.1	8.07±0.236	2.9	0.9	89.8
150	157±3.25	2.1	4.7	156±5.61	3.6	4.0	/
800	829±15.7	1.9	3.6	807±26.8	3.3	0.9	93.1
1500	1480±9.83	0.7	?1.3	1440±58.3	4.0	?4.0	89.5

Items	Condition	Result
Plasma sample	Place at room temperature for 18.7 hours	Good
	5 freeze-thaw cycles at ?20 ℃/?70 ℃
	Freeze for 50 days at ?20 ℃/?70 ℃ for a long time
Supernatant after plasma sample processing	Place in the automatic sampler at 8 ℃ for 5 days
Stock solution	Place at room temperature for 16.2 hours
	Place at ?20 ℃ for 16 days
	Place at ?20 ℃ for 43 days
Working solution	Place at room temperature for 15.8 hours
Working solution	Place at ?20 ℃ for 15 days

盐酸达拉他韦片在中国健康受试者中的生物等效性研究

Study on bioequivalence evaluation of daclatasvir hydrochloride tablets in healthy Chinese subjects

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参考文献 20

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Metrics

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Parameters	Fasting		Fed
	$ \overline{x} $±s (%CV)		$ \overline{x} $±s (%CV)
	Test (n=29)	Reference (n=30)	Test (n=30)	Reference (n=30)
T_max (h)*	1.500 (1.000,4.005)	1.000 (0.750,2.500)	2.000 (0.750,6.000)	2.000 (0.750,6.000)
C_max (ng/mL)	1102.690±311.345 (28.235)	1174.800±361.642 (30.783)	791.733±230.334 (29.092)	872.000±303.921 (34.853)
AUC_0-t (h·ng·mL^?1)	13517.051±3576.349 (26.458)	13503.448±4022.914 (29.792)	10974.708±3213.564 (29.282)	11217.253±4060.319 (36.197)
AUC_0-∞ (h·ng·mL^?1)	13672.052±3626.297 (26.523)	13669.602±4059.563 (29.698)	11140.018±3261.934 (29.281)	11396.162±4143.077 (36.355)
t_1/2 (h)	10.825±1.167 (10.777)	10.778±1.294 (12.003)	10.777±1.961 (18.201)	10.761±1.969 (18.299)
λ_z (1/h)	0.065±0.007 (11.242)	0.065±0.008 (12.563)	0.066±0.010 (15.690)	0.066±0.010 (14.792)

Parameters	Fasting						Fed
	Geometric means and ratios (n=30)			%CV	90%CI	Power%	Geometric means and ratios (n=30)			%CV	90%CI	Power%
	T	R	T/R%	%CV	90%CI	Power%	T	R	T/R%	%CV	90%CI	Power%
C_max (ng/mL)	1055.015	1121.908	94.0%	13.59%	88.52%-99.90%	99.74%	759.279	824.366	92.1%	28.53%	81.46%-104.15%	59.53%
AUC_0-t (h·ng·mL^?1)	12837.120	12922.410	99.3%	11.22%	94.50%-104.43%	>99.99%	10508.669	10575.375	99.4%	16.65%	92.41%-106.86%	99.94%
AUC_0-∞ (h·ng·mL^?1)	12986.587	13088.394	99.2%	11.14%	94.42%-104.27%	>99.99%	10667.079	10739.659	99.3%	16.63%	92.37%-106.80%	99.94%

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