Accumulation of major linezolid metabolites in patients with renal impairment

Ernane Souza; Ryan L. Crass; Jeremy Felton; Kengo Hanaya; Manjunath P. Pai

doi:10.1128/AAC.00027-20

Accumulation of major linezolid metabolites in patients with renal impairment

Ernane Souza, Ryan L. Crass, Jeremy Felton, Kengo Hanaya, Manjunath P. Pai

School of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

In patients with renal impairment (n=22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher, respectively, than in patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated with linezolid concentrations (r² = 0.26 for PNU-142300 and 0.06 for PNU-142586). Linezolid and its metabolites share potential toxicophores that deserve characterization to mitigate higher myelosuppression risk in patients with renal impairment.

Original language	English
Article number	e00027-20
Journal	Antimicrobial Agents and Chemotherapy
Volume	64
Issue number	5
DOIs	https://doi.org/10.1128/AAC.00027-20
Publication status	Published - 2020 May 1

Keywords

Dialysis
Myelosuppression
Oxazolidinones
Pharmacodynamics
Toxicology

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/AAC.00027-20

Cite this

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title = "Accumulation of major linezolid metabolites in patients with renal impairment",

abstract = "In patients with renal impairment (n=22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher, respectively, than in patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated with linezolid concentrations (r2 = 0.26 for PNU-142300 and 0.06 for PNU-142586). Linezolid and its metabolites share potential toxicophores that deserve characterization to mitigate higher myelosuppression risk in patients with renal impairment.",

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note = "Funding Information: This study was supported through start-up funds from the University of Michigan to M.P.P. We have no conflicts of interest to declare. Publisher Copyright: {\textcopyright} 2020 American Society for Microbiology. All Rights Reserved.",

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AU - Souza, Ernane

AU - Crass, Ryan L.

AU - Felton, Jeremy

AU - Hanaya, Kengo

AU - Pai, Manjunath P.

N1 - Funding Information: This study was supported through start-up funds from the University of Michigan to M.P.P. We have no conflicts of interest to declare. Publisher Copyright: © 2020 American Society for Microbiology. All Rights Reserved.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - In patients with renal impairment (n=22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher, respectively, than in patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated with linezolid concentrations (r2 = 0.26 for PNU-142300 and 0.06 for PNU-142586). Linezolid and its metabolites share potential toxicophores that deserve characterization to mitigate higher myelosuppression risk in patients with renal impairment.

AB - In patients with renal impairment (n=22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher, respectively, than in patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated with linezolid concentrations (r2 = 0.26 for PNU-142300 and 0.06 for PNU-142586). Linezolid and its metabolites share potential toxicophores that deserve characterization to mitigate higher myelosuppression risk in patients with renal impairment.

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KW - Oxazolidinones

KW - Pharmacodynamics

KW - Toxicology

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Accumulation of major linezolid metabolites in patients with renal impairment

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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