Randomized, Double-Blind, Placebo-Controlled Studies of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eravacycline

Antimicrobial Agents and Chemotherapy
Joseph V NewmanLarry Tsai

Abstract

Eravacycline is a novel, fully synthetic fluorocycline antibiotic with in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative pathogens, including multidrug-resistant (MDR) bacteria. The pharmacokinetics (PK), urinary excretion, and safety/tolerability of intravenous (i.v.) eravacycline were evaluated in single- and multiple-ascending-dose studies. Healthy subjects received single i.v. doses of 0.1 to 3 mg/kg of body weight or 10 days of treatment with 0.5 or 1.5 mg/kg every 24 h (q24h) over 30 min, 1.5 mg/kg q24h over 60 min, or 1 mg/kg q12h over 60 min. After single doses, total exposure (the area under the plasma concentration-time curve [AUC]) and the maximum plasma concentrations (Cmax) of eravacycline increased in an approximately dose-proportional manner. After multiple doses, steady state was achieved within 5 to 7 days. Accumulation ranged from approximately 7% to 38% with the q24h dosing regimens and was 45% with 1 mg/kg q12h. Eravacycline was generally well tolerated, with dose-related nausea, infusion site effects, and superficial phlebitis that were mild or moderate occurring. These results provide support for the 1-mg/kg q12h regimen used in clinical studies of eravacycline.

References

Dec 24, 2004·Antimicrobial Agents and Chemotherapy·Gopal MuralidharanSteven Troy
Jul 4, 2006·The Journal of Antimicrobial Chemotherapy·Kenneth N Agwuh, Alasdair MacGowan
Sep 4, 2009·Clinical Pharmacokinetics·April BarbourHartmut Derendorf
Sep 15, 2009·Diagnostic Microbiology and Infectious Disease·Julie PassarellEvelyn J Ellis-Grosse
Oct 5, 2011·Antimicrobial Agents and Chemotherapy·Christopher M RubinoPaul G Ambrose
Feb 23, 2012·Antimicrobial Agents and Chemotherapy·Trudy H GrossmanJoyce A Sutcliffe
Aug 28, 2013·Antimicrobial Agents and Chemotherapy·J A SutcliffeT H Grossman
Feb 6, 2014·Biological Chemistry·Fabian NguyenDaniel N Wilson
Feb 11, 2016·Drugs·George G ZhanelJames A Karlowsky
Apr 6, 2016·Antimicrobial Agents and Chemotherapy·David M LivermoreNeil Woodford
Jun 30, 2016·Antimicrobial Agents and Chemotherapy·Marguerite L MonogueDavid P Nicolau
Jul 15, 2017·International Journal of Antimicrobial Agents·Harald SeifertPaul G Higgins
Nov 22, 2017·Antimicrobial Agents and Chemotherapy·Jolene K BergStephen Villano

❮ Previous
Next ❯

Citations

Dec 19, 2018·Antimicrobial Agents and Chemotherapy·Joseph V NewmanLarry Tsai
Dec 19, 2018·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Joseph S SolomkinLarry Tsai
Jul 3, 2019·Journal of Clinical Medicine·Nicola PetrosilloGuido Granata
Jun 9, 2019·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Young Ran Lee, Caitlin Elizabeth Burton
Nov 28, 2019·Clinical Pharmacokinetics·Keith A RodvoldManjunath P Pai
Apr 23, 2019·Expert Review of Anti-infective Therapy·Georgios L VoulgarisMatthew E Falagas
May 3, 2019·Clinical Pharmacokinetics·Matthew W McCarthy
Sep 16, 2020·The Journal of Antimicrobial Chemotherapy·Anthony M BuckleyMark H Wilcox
Aug 20, 2019·Indian Journal of Medical Microbiology·Balaji VeeraraghavanBalasubramanian Sundaram
Jan 1, 2019·Indian Journal of Medical Microbiology·Balaji VeeraraghavanBalasubramanian Sundaram
Oct 17, 2020·Infectious Diseases and Therapy·Nicholas Van HiseApoorv Kalra
Oct 28, 2021·International Journal of Antimicrobial Agents·Wei YuYunqing Qiu
Dec 2, 2021·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Andrei ZidaruVincent H Tam

❮ Previous
Next ❯

Methods Mentioned

BETA
pregnancy test

Software Mentioned

WinNonlin Enterprise
Phoenix WinNonlin

Related Concepts

Related Feeds

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.