当前位置： SCI文献检索 > ANTIMICROBIAL AGENTS AND CHEMOTHERAPY期刊下所有文献 > Safety, tolerability, and pharmacokinetics of intravenous nemonoxacin in healthy chinese volunteers.

Safety, tolerability, and pharmacokinetics of intravenous nemonoxacin in healthy chinese volunteers.

Abstract：

: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 μg/ml, 7.152 μg/ml, and 11.029 μg/ml, respectively. The corresponding values for the area under the concentration-time curve from 0 to 72 hours (AUC0-72 h) were 17.05 μg · h/ml, 39.30 μg · h/ml, and 61.98 μg · 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-∞. 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.).

journal_name

Antimicrob Agents Chemother

journal_title

Antimicrobial agents and chemotherapy

authors

Cao GY,Zhang J,Zhang YY,Guo BN,Yu JC,Wu XJ,Chen YC,Wu JF,Shi YG

doi

10.1128/AAC.02972-14

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

6116-21

issue

eissn

0066-4804

issn

1098-6596

pii

AAC.02972-14

journal_volume

pub_type

杂志文章,随机对照试验

在线工具

Safety, tolerability, and pharmacokinetics of intravenous nemonoxacin in healthy chinese volunteers.