PMID- 30224529
OWN - NLM
STAT- MEDLINE
DCOM- 20191023
LR  - 20221207
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 62
IP  - 12
DP  - 2018 Dec
TI  - A Randomized Study of the Single-Dose Safety, Pharmacokinetics, and Food Effect 
      of Chinfloxacin and Its Effect on Thorough QT/QTc Interval in Healthy Chinese 
      Volunteers.
LID - 10.1128/AAC.01087-18 [doi]
LID - e01087-18
AB  - Chinfloxacin hydrochloride is a novel tricyclic fluorinated quinolone in 
      development for treatment of conventional and biothreat infections. This 
      first-in-human randomized study in Chinese healthy subjects was divided into 5 
      parts. Part A was a single-ascending-dose study to assess safety and tolerability 
      of chinfloxacin. The single-dose pharmacokinetic study, a food effect study, and 
      a multiple-dose pharmacokinetics study were conducted in parts B, C, and D, 
      respectively. Part E was a randomized, placebo-controlled and positive-control 
      single-dose, crossover study to evaluate the effect of chinfloxacin on thorough 
      electrocardiographic QT/corrected QT (QTc) interval. The results suggest that 
      single and multiple oral administrations of chinfloxacin were well tolerated. The 
      observed adverse events (AEs) were dizziness, nausea, weakness, photosensitive 
      dermatitis, and increased frequency of defecation. All AEs were mild and were 
      resolved spontaneously without any treatment. The time to peak plasma 
      concentration (T(max) and C(max), respectively) was about 2 h, and the half-life 
      was 14 to 16 h. Food slightly affected the drug's rate and extent of absorption, 
      increasing the T(max) from 1.60 to 2.59 h and reducing the C(max) by 13.6% and 
      area under the concentration-time curve by 8.95%. Chinfloxacin at 400 mg had no 
      effect on prolongation of QT/QTc intervals. Although 600 mg chinfloxacin had a 
      mild effect on the prolongation of the QT/QTc interval, the effect was less 
      pronounced than that of the positive control, 400 mg moxifloxacin. The 
      pharmacokinetics and safety profiles of chinfloxacin in healthy Chinese 
      volunteers support its once-daily dosing in future clinical investigations. (This 
      study has been registered at www.ChiCTR.org.cn under identifiers 
      ChiCTR-TRC-10001619 for parts A to D and ChiCTR1800015906 for part E.).
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Zhao, Caiyun
AU  - Zhao C
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Lv, Yuan
AU  - Lv Y
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China lucy4869@sohu.com.
FAU - Wei, Minji
AU  - Wei M
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Li, Xiangyan
AU  - Li X
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Hou, Fang
AU  - Hou F
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Wang, Jin
AU  - Wang J
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Ma, Xuzhu
AU  - Ma X
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Kang, Zisheng
AU  - Kang Z
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Mao, Wei
AU  - Mao W
AD  - XinChang Factory, Zhejiang Pharmaceutical Co., Ltd., Zhejiang, China.
FAU - Liu, Yan
AU  - Liu Y
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Xia, Yahong
AU  - Xia Y
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
FAU - Tian, Jihong
AU  - Tian J
AD  - Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, 
      China.
LA  - eng
SI  - ChiCTR/ChiCTR-TRC-10001619
SI  - ChiCTR/ChiCTR1800015906
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20181126
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Fluoroquinolones)
RN  - 0 (chinfloxacin)
RN  - U188XYD42P (Moxifloxacin)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Anti-Bacterial Agents/adverse effects/blood/*pharmacokinetics
MH  - Asian People
MH  - Cross-Over Studies
MH  - Dermatitis/etiology/physiopathology
MH  - Dizziness/chemically induced/physiopathology
MH  - Drug Administration Schedule
MH  - Drug Dosage Calculations
MH  - Eating/physiology
MH  - Electrocardiography
MH  - Fatigue/chemically induced/physiopathology
MH  - Female
MH  - Fluoroquinolones/adverse effects/blood/*pharmacokinetics
MH  - Food-Drug Interactions
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Heart/*drug effects/physiology
MH  - Humans
MH  - Male
MH  - Moxifloxacin/adverse effects/blood/pharmacokinetics
MH  - Nausea/chemically induced/physiopathology
MH  - Patient Safety
PMC - PMC6256790
OTO - NOTNLM
OT  - chinfloxacin hydrochloride
OT  - healthy Chinese volunteers
OT  - pharmacokinetics
OT  - safety
OT  - thorough QT study
OT  - tolerability
EDAT- 2018/09/19 06:00
MHDA- 2019/10/24 06:00
PMCR- 2019/05/26
CRDT- 2018/09/19 06:00
PHST- 2018/05/25 00:00 [received]
PHST- 2018/09/06 00:00 [accepted]
PHST- 2018/09/19 06:00 [pubmed]
PHST- 2019/10/24 06:00 [medline]
PHST- 2018/09/19 06:00 [entrez]
PHST- 2019/05/26 00:00 [pmc-release]
AID - AAC.01087-18 [pii]
AID - AAC01087-18 [pii]
AID - 10.1128/AAC.01087-18 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2018 Nov 26;62(12):e01087-18. doi: 
      10.1128/AAC.01087-18. Print 2018 Dec.