PMID- 25092690
OWN - NLM
STAT- MEDLINE
DCOM- 20150520
LR  - 20211021
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 58
IP  - 10
DP  - 2014 Oct
TI  - Safety, tolerability, and pharmacokinetics of intravenous nemonoxacin in healthy 
      chinese volunteers.
PG  - 6116-21
LID - 10.1128/AAC.02972-14 [doi]
AB  - Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent 
      broad-spectrum activity against Gram-positive, Gram-negative, and atypical 
      pathogens, including vancomycin-nonsusceptible methicillin-resistant 
      Staphylococcus aureus (MRSA), quinolone-resistant MRSA, quinolone-resistant 
      Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and 
      erythromycin-resistant S. pneumoniae. This first-in-human study was aimed at 
      assessing the safety, tolerability, and pharmacokinetic properties of intravenous 
      nemonoxacin in healthy Chinese volunteers. The study comprised a randomized, 
      double-blind, placebo-controlled, dose escalating safety and tolerability study 
      in 92 subjects and a randomized, single-dose, open-label, 3-period Latin-square 
      crossover pharmacokinetic study in 12 subjects. The study revealed that 
      nemonoxacin infusion was well tolerated up to the maximum dose of 1,250 mg, and 
      the acceptable infusion rates ranged from 0.42 to 5.56 mg/min. Drug-related 
      adverse events (AEs) were mild, transient, and confined to local irritation at 
      the injection site. The pharmacokinetic study revealed that after the 
      administration of 250, 500, and 750 mg of intravenous nemonoxacin, the maximum 
      plasma drug concentration (Cmax) values were 4.826 mug/ml, 7.152 mug/ml, and 11.029 
      mug/ml, respectively. The corresponding values for the area under the 
      concentration-time curve from 0 to 72 hours (AUC0-72 h) were 17.05 mug . h/ml, 
      39.30 mug . h/ml, and 61.98 mug . h/ml. The mean elimination half-life (t1/2) was 
      11 h, and the mean cumulative drug excretion rate within 72 h ranged from 64.93% 
      to 77.17%. Volunteers treated with 250 to 750 mg nemonoxacin exhibited a linear 
      dose-response relationship between the AUC0-72 h and AUC0-infinity. These findings 
      provide further support for the safety, tolerability, and pharmacokinetic 
      properties of intravenous nemonoxacin. (This study has been registered at 
      ClinicalTrials.gov under registration no. NCT01944774.).
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Cao, Guo-Ying
AU  - Cao GY
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key 
      Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family 
      Planning Commission, Shanghai, China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key 
      Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family 
      Planning Commission, Shanghai, China zhangj_fudan@aliyun.com.
FAU - Zhang, Ying-Yuan
AU  - Zhang YY
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key 
      Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family 
      Planning Commission, Shanghai, China.
FAU - Guo, Bei-Ning
AU  - Guo BN
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key 
      Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family 
      Planning Commission, Shanghai, China.
FAU - Yu, Ji-Cheng
AU  - Yu JC
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key 
      Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family 
      Planning Commission, Shanghai, China.
FAU - Wu, Xiao-Jie
AU  - Wu XJ
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key 
      Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family 
      Planning Commission, Shanghai, China.
FAU - Chen, Yuan-Cheng
AU  - Chen YC
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key 
      Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family 
      Planning Commission, Shanghai, China.
FAU - Wu, Ju-Fang
AU  - Wu JF
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Shi, Yao-Guo
AU  - Shi YG
AD  - Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China Key 
      Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family 
      Planning Commission, Shanghai, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT01944774
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140804
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Quinolones)
RN  - P94L0PVO94 (nemonoxacin)
SB  - IM
MH  - Administration, Intravenous
MH  - Anti-Bacterial Agents/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Double-Blind Method
MH  - Healthy Volunteers
MH  - Humans
MH  - Quinolones/administration & dosage/*adverse effects/*pharmacokinetics
PMC - PMC4187916
EDAT- 2014/08/06 06:00
MHDA- 2015/05/21 06:00
PMCR- 2015/04/01
CRDT- 2014/08/06 06:00
PHST- 2014/08/06 06:00 [entrez]
PHST- 2014/08/06 06:00 [pubmed]
PHST- 2015/05/21 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - AAC.02972-14 [pii]
AID - 02972-14 [pii]
AID - 10.1128/AAC.02972-14 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2014 Oct;58(10):6116-21. doi: 10.1128/AAC.02972-14. 
      Epub 2014 Aug 4.