Population Pharmacokinetic Model-Based Optimization of Linezolid Dosing in Hematooncological Patients With Suspected or Proven Gram-Positive Sepsis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10503198" target="_blank" >RIV/00179906:_____/25:10503198 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10503198 RIV/00216208:11150/25:10503198 RIV/00064165:_____/25:10503198

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rT1XiHg5ZD" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rT1XiHg5ZD</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/cts.70346" target="_blank" >10.1111/cts.70346</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Population Pharmacokinetic Model-Based Optimization of Linezolid Dosing in Hematooncological Patients With Suspected or Proven Gram-Positive Sepsis

Popis výsledku v původním jazyce

The objective of this study was to develop a population pharmacokinetic model for linezolid in hematooncological patients with sepsis, and to propose dosing optimization based on pharmacokinetic covariates that would lead to improved achievement of the PK/PD target. Therapeutic drug monitoring data from hematooncological patients treated with linezolid for suspected or proven sepsis were analyzed. A pharmacokinetic population model for linezolid was constructed using a nonlinear mixed-effects modeling approach. Monte Carlo simulations were then used to compare various dosing regimens in terms of PK/PD target attainment. A total of 197 linezolid serum concentrations obtained from 22 patients were included in the analysis. Patients&apos; age was found to be the most predictive covariate for linezolid pharmacokinetics. In a patient with a median age of 59 years, the volume of distribution and clearance of linezolid were 46.2 L and 12.1 L/h, respectively. During the first 4 days of therapy, linezolid clearance decreased by 33%. The probability of PK/PD target attainment increased through the individualization of the dose according to the patient&apos;s age, administration of a loading dose, and administration of linezolid via continuous infusion. For this scenario, an easy-to-use nomogram was designed.

Název v anglickém jazyce

Population Pharmacokinetic Model-Based Optimization of Linezolid Dosing in Hematooncological Patients With Suspected or Proven Gram-Positive Sepsis

Popis výsledku anglicky

The objective of this study was to develop a population pharmacokinetic model for linezolid in hematooncological patients with sepsis, and to propose dosing optimization based on pharmacokinetic covariates that would lead to improved achievement of the PK/PD target. Therapeutic drug monitoring data from hematooncological patients treated with linezolid for suspected or proven sepsis were analyzed. A pharmacokinetic population model for linezolid was constructed using a nonlinear mixed-effects modeling approach. Monte Carlo simulations were then used to compare various dosing regimens in terms of PK/PD target attainment. A total of 197 linezolid serum concentrations obtained from 22 patients were included in the analysis. Patients&apos; age was found to be the most predictive covariate for linezolid pharmacokinetics. In a patient with a median age of 59 years, the volume of distribution and clearance of linezolid were 46.2 L and 12.1 L/h, respectively. During the first 4 days of therapy, linezolid clearance decreased by 33%. The probability of PK/PD target attainment increased through the individualization of the dose according to the patient&apos;s age, administration of a loading dose, and administration of linezolid via continuous infusion. For this scenario, an easy-to-use nomogram was designed.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinical and Translational Science

ISSN

1752-8054

e-ISSN

1752-8062

Svazek periodika

18

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

e70346

Kód UT WoS článku

001563452800001

EID výsledku v databázi Scopus

2-s2.0-105015328278