TY - JOUR
T1 - Eravacycline pharmacokinetics and challenges in defining humanized exposure in vivo
AU - Thabit, Abrar K.
AU - Monogue, Marguerite L.
AU - Nicolau, David P.
N1 - Funding Information:
This project was funded in part by Tetraphase Pharmaceuticals, Inc., and in part with federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under contract HHSO100201200002C. D.P.N. is a member of the scientific board of Tetraphase Pharmaceuticals, Inc., and has received research support from Tetraphase Pharmaceuticals, Inc. The other authors have nothing to disclose. We thank Jared Crandon, Lucinda Lamb, Jennifer Tabor-Rennie, Sara Robinson, Debora Santini, Christina Sutherland, Kimelyn Greenwood, Yukihiro Hamada, Islam Ghazi, Wonhee So, and Jaime Verastegui from the Center for Anti-Infective Research and Development, Hartford, CT, for their assistance with the conduct of this study and Jack Wang and Abdul Mutlib from Frontage Laboratories, Inc., Exton, PA, for analysis of eravacycline concentrations. This work, including the efforts of David P. Nicolau, was funded by Biomedical Advanced Research and Development, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services (HHSO100201200002C). This work, including the efforts of David P. Nicolau, was funded by Tetraphase Pharmaceuticals, Inc. This project has been funded in part by Tetraphase Pharmaceuticals, Inc., and in part with federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under contract no. HHSO100201200002C.
Publisher Copyright:
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016/8
Y1 - 2016/8
N2 - We assessed the pharmacokinetic profile of eravacycline, a novel antibiotic of the tetracycline class, and determined the dose in an immunocompetent murine thigh infection model that would provide free-drug exposure similar to that observed in humans after the administration of 1 mg/kg intravenously (i.v.) every 12 h (q12h). Eravacycline demonstrated a nonlinear protein-binding profile. The 2.5-mg/kg i.v. q12h dose in mice resulted in an area under the concentration-time curve for the free, unbound fraction of the drug of 1.64 mg·h/liter, which closely resembles the human exposure level.
AB - We assessed the pharmacokinetic profile of eravacycline, a novel antibiotic of the tetracycline class, and determined the dose in an immunocompetent murine thigh infection model that would provide free-drug exposure similar to that observed in humans after the administration of 1 mg/kg intravenously (i.v.) every 12 h (q12h). Eravacycline demonstrated a nonlinear protein-binding profile. The 2.5-mg/kg i.v. q12h dose in mice resulted in an area under the concentration-time curve for the free, unbound fraction of the drug of 1.64 mg·h/liter, which closely resembles the human exposure level.
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U2 - 10.1128/AAC.00240-16
DO - 10.1128/AAC.00240-16
M3 - Article
C2 - 27353264
AN - SCOPUS:84979257041
SN - 0066-4804
VL - 60
SP - 5072
EP - 5075
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 8
ER -