PMID- 32801649
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20221207
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 14
DP  - 2020
TI  - Bioequivalence Study of Amitriptyline Hydrochloride Tablets in Healthy Chinese 
      Volunteers Under Fasting and Fed Conditions.
PG  - 3131-3142
LID - 10.2147/DDDT.S258173 [doi]
AB  - PURPOSE: This study compares the pharmacokinetic and safety profiles between a 
      new generic and a branded reference formulation of amitriptyline hydrochloride 
      tablets, and assesses the bioequivalence of the two products in healthy Chinese 
      volunteers to obtain sufficient evidence for the marketing approval of the 
      generic drug. MATERIALS AND METHODS: A randomized, open-label, two-period 
      crossover study (clinicaltrials.gov, NCT03646526) was conducted under both 
      fasting and fed conditions in healthy Chinese volunteers (24 subjects/condition). 
      Eligible subjects randomly received a single 25 mg dose of either the test or the 
      reference formulation, followed by a 3-week washout period. Blood samples were 
      collected until 144 h following administration. The pharmacokinetic parameters 
      were acquired based on the concentration-time profiles, including the areas under 
      the plasma concentration-time curve (AUC(0-t), AUC(0-infinity)), the peak plasma 
      concentration (C(max)), the time to achieve C(max) (T(max)), and the elimination 
      half-life (t(1/2)). The geometric mean ratios (GMRs) and the corresponding 90% 
      confidence intervals (CIs) of amitriptyline were acquired for bioequivalence 
      analysis, and values of these parameters for nortriptyline were used for 
      comparison of therapeutic outcomes. Safety assessments included laboratory tests, 
      physical examination, vital signs, and incidence of adverse events (AEs). 
      RESULTS: The values of t(1/2) and T(max) for amitriptyline were not significantly 
      different between the test and reference products under both fasting and fed 
      conditions (P > 0.05). The GMRs of C(max), AUC(0-t), and AUC(0-infinity) between the two 
      products, and corresponding 90% CIs, were all within the range of 80% to 125% 
      under both fasting and fed conditions. The test and reference products were well 
      tolerated and did not elicit serious adverse events. CONCLUSION: This study 
      demonstrated that the generic and reference products were well tolerated by the 
      subjects and bioequivalent, according to the rate and extent of the drug 
      absorption.
CI  - (c) 2020 Zhai et al.
FAU - Zhai, You
AU  - Zhai Y
AUID- ORCID: 0000-0002-7972-1462
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
FAU - Wu, Lihua
AU  - Wu L
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
FAU - Zheng, Yunliang
AU  - Zheng Y
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
FAU - Wu, Minglan
AU  - Wu M
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
FAU - Huang, Yujie
AU  - Huang Y
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
FAU - Huang, Qian
AU  - Huang Q
AUID- ORCID: 0000-0001-6409-709X
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
FAU - Shentu, Jianzhong
AU  - Shentu J
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
AD  - College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
FAU - Zhao, Qingwei
AU  - Zhao Q
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
FAU - Liu, Jian
AU  - Liu J
AUID- ORCID: 0000-0001-6882-0468
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, People's Republic of China.
AD  - Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The 
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      People's Republic of China.
LA  - eng
SI  - ClinicalTrials.gov/NCT03646526
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20200804
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Drugs, Generic)
RN  - 0 (Tablets)
RN  - 1806D8D52K (Amitriptyline)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Amitriptyline/administration & dosage/blood/*pharmacokinetics/*therapeutic use
MH  - Area Under Curve
MH  - Asian People
MH  - Cross-Over Studies
MH  - Drug Tolerance
MH  - Drugs, Generic/administration & dosage/*pharmacokinetics/*therapeutic use
MH  - *Fasting
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Tablets
MH  - Therapeutic Equivalency
MH  - Young Adult
PMC - PMC7414938
OTO - NOTNLM
OT  - amitriptyline hydrochloride
OT  - bioequivalence
OT  - nortriptyline
OT  - pharmacokinetics
COIS- Hunan Dongting Pharmaceutical Co., Ltd. (Hunan, China) funded our study, which 
      was the manufacturer of amitriptyline hydrochloride tablets. The funder had not 
      any influence on data collection and analysis, manuscript preparation, and 
      decision to publish. All authors report no conflicts of interest in this work.
EDAT- 2020/08/18 06:00
MHDA- 2021/07/02 06:00
PMCR- 2020/08/04
CRDT- 2020/08/18 06:00
PHST- 2020/04/21 00:00 [received]
PHST- 2020/07/17 00:00 [accepted]
PHST- 2020/08/18 06:00 [entrez]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/08/04 00:00 [pmc-release]
AID - 258173 [pii]
AID - 10.2147/DDDT.S258173 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2020 Aug 4;14:3131-3142. doi: 10.2147/DDDT.S258173. 
      eCollection 2020.