PMID- 31571834 OWN - NLM STAT- MEDLINE DCOM- 20200225 LR - 20220410 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 13 DP - 2019 TI - Bioequivalence Study Of A Fixed-Dose Combination Tablet Containing Melitracen 10 mg And Flupentixol 0.5 mg In Healthy Chinese Volunteers Under Fasted And Fed Conditions. PG - 3331-3342 LID - 10.2147/DDDT.S207561 [doi] AB - PURPOSE: A fixed-dose combination (FDC) tablet of melitracen/flupentixol has been widely used for depression. The purpose of this study was to assess the safety profile and the relative bioavailability of two FDC products containing 10 mg melitracen and 0.5 mg flupentixol from two different manufacturers, in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation. METHODS: The study was designed as a single-dose, randomized, open-label, 2-period crossover study under fasted or fed conditions in healthy Chinese subjects. Twenty-four subjects (16 men and 8 women) were selected for fasted study, and another 24 cases (16 men and 8 women) were in fed study. Each subject was randomized at the beginning to receive either a single dose of the reference FDC or the test FDC tablet during the first period. Following two-week washout period, all subjects received the alternate formulation during the second period. Blood samples were collected up to 144 hrs after administration. Pharmacokinetic parameters, including C(max), T(max), AUC(0-t), AUC(0-infinity), t(1/2), CL/F, and V(d)/F were acquired based on the time versus concentration profiles. Then, the geometric mean ratios (GMR) and corresponding 90% CIs were calculated for the determination of bioequivalence analysis. Safety assessment included changes in vital signs and laboratory tests, physical examination findings, and incidence or reports of adverse events (AEs). RESULTS: The present study has clearly indicated the test and the reference FDC products are bioequivalent in terms of rate and extent of drug absorption. GMR of C(max), AUC(0-t), and AUC(0-infinity) for both flupentixol and melitracen between the two formulation FDC products, and corresponding 90% CIs, were all within the range of 80% to 125% under fasted or fed conditions. Both the test and the reference FDC products indicated good tolerance in all volunteers. Chinese Clinical Trials Registry identifier: CTR20171256. CI - (c) 2019 Wu et al. FAU - Wu, Lihua AU - Wu L AUID- ORCID: 0000-0001-6620-1858 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 - Xu, Chang AU - Xu C 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, Guolan AU - Wu G 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 - Zhou, Huili AU - Zhou H 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 - Lv, Duo AU - Lv D 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 - Zhai, You AU - Zhai 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, 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 - Tang, Wenling AU - Tang W AD - College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. FAU - Li, Fangqiong AU - Li F AD - Clinical Research Department, Haisco Pharmaceutical Group, Sichuan, 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. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20190919 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Anthracenes) RN - 0 (Antidepressive Agents) RN - 0 (Drug Combinations) RN - 0 (Tablets) RN - 0 (flupentixol, melitracen drug combination) RN - FA0UYH6QUO (Flupenthixol) SB - IM MH - Adult MH - Anthracenes/administration & dosage/adverse effects/*pharmacokinetics MH - Antidepressive Agents/administration & dosage/adverse effects/*pharmacokinetics MH - Area Under Curve MH - China MH - Cross-Over Studies MH - Drug Combinations MH - Fasting MH - Female MH - Flupenthixol/administration & dosage/adverse effects/*pharmacokinetics MH - Healthy Volunteers MH - Humans MH - Male MH - Tablets MH - Therapeutic Equivalency MH - Young Adult PMC - PMC6756841 OTO - NOTNLM OT - bioequivalence OT - fixed-dose combination tablet OT - flupentixol OT - melitracen OT - pharmacokinetics COIS- The authors report no con fl icts of interest in this work. EDAT- 2019/10/02 06:00 MHDA- 2020/02/26 06:00 PMCR- 2019/09/19 CRDT- 2019/10/02 06:00 PHST- 2019/03/11 00:00 [received] PHST- 2019/08/29 00:00 [accepted] PHST- 2019/10/02 06:00 [entrez] PHST- 2019/10/02 06:00 [pubmed] PHST- 2020/02/26 06:00 [medline] PHST- 2019/09/19 00:00 [pmc-release] AID - 207561 [pii] AID - 10.2147/DDDT.S207561 [doi] PST - epublish SO - Drug Des Devel Ther. 2019 Sep 19;13:3331-3342. doi: 10.2147/DDDT.S207561. eCollection 2019.