Pharmacodynamic target assessment and prediction of clinically effective dosing regimen of TP0586532, a novel non-hydroxamate LpxC inhibitor, using a murine lung infection model

Autor: Kiyoko Fujita, Iichiro Takata, Ippei Yoshida, Yusuke Honma, Hirotoshi Okumura, Katsumasa Otake, Hajime Takashima, Hiroyuki Sugiyama
Rok vydání: 2021
Předmět:
Zdroj: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 28(5)
ISSN: 1437-7780
Popis: TP0586532 is a novel non-hydroxamate UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) inhibitor. Pharmacokinetic/pharmacodynamic (PK/PD) indices and magnitude of index that correlated with the efficacy of TP0586532 were determined and used to estimate the clinically effective doses of TP0586532.Dose-fractionation studies were conducted using a murine neutropenic lung infection model caused by carbapenem-resistant Enterobacteriaceae. The relationships between the efficacy and the PK/PD index (the maximum unbound plasma concentration divided by the MIC [fCThe PK/PD index that best correlated with the efficacy was the fCThese results indicate the potential for TP0586532 to have clinical efficacy at reasonable doses against infections caused by carbapenem-resistant Enterobacteriaceae. This study provided helpful information for a clinically effective dosing regimen of TP0586532.
Databáze: OpenAIRE
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