Dosing Optimization of Posaconazole in Lung-Transplant Recipients Based on Population Pharmacokinetic Model

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F23%3A10469166" target="_blank" >RIV/00064165:_____/23:10469166 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/23:10469166 RIV/00216208:11110/23:10469166 RIV/00064203:_____/23:10469166

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YvM1ukmXeH" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YvM1ukmXeH</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/antibiotics12091399" target="_blank" >10.3390/antibiotics12091399</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dosing Optimization of Posaconazole in Lung-Transplant Recipients Based on Population Pharmacokinetic Model

Popis výsledku v původním jazyce

Although posaconazole tablets show relatively low variability in pharmacokinetics (PK), the proportion of patients achieving the PK/PD target at the approved uniform dose for both prophylaxis and therapy is not satisfactory. The aim of this study was to develop a posaconazole population PK model in lung-transplant recipients and to propose a covariate-based dosing optimization for both prophylaxis and therapy. In this prospective study, 80 posaconazole concentrations obtained from 32 lung-transplant patients during therapeutic drug monitoring were analyzed using nonlinear mixed-effects modelling, and a Monte Carlo simulation was used to describe the theoretical distribution of posaconazole PK profiles at various dosing regimens. A one-compartment model with both linear absorption and elimination best fit the concentration-time data. The population apparent volume of distribution was 386.4 L, while an apparent clearance of 8.8 L/h decreased by 0.009 L/h with each year of the patient&apos;s age. Based on the covariate model, a dosing regimen of 200 mg/day for prophylaxis in patients &gt;60 years, 300 mg/day for prophylaxis in patients &lt;60 years and for therapy in patients &gt;60 years, and 400 mg/day for therapy in patients &lt;60 years has been proposed. At this dosing regimen, the PK/PD target for prophylaxis and therapy is reached in 95% and 90% of population, respectively, representing significantly improved outcomes in comparison with the uniform dose.

Název v anglickém jazyce

Dosing Optimization of Posaconazole in Lung-Transplant Recipients Based on Population Pharmacokinetic Model

Popis výsledku anglicky

Although posaconazole tablets show relatively low variability in pharmacokinetics (PK), the proportion of patients achieving the PK/PD target at the approved uniform dose for both prophylaxis and therapy is not satisfactory. The aim of this study was to develop a posaconazole population PK model in lung-transplant recipients and to propose a covariate-based dosing optimization for both prophylaxis and therapy. In this prospective study, 80 posaconazole concentrations obtained from 32 lung-transplant patients during therapeutic drug monitoring were analyzed using nonlinear mixed-effects modelling, and a Monte Carlo simulation was used to describe the theoretical distribution of posaconazole PK profiles at various dosing regimens. A one-compartment model with both linear absorption and elimination best fit the concentration-time data. The population apparent volume of distribution was 386.4 L, while an apparent clearance of 8.8 L/h decreased by 0.009 L/h with each year of the patient&apos;s age. Based on the covariate model, a dosing regimen of 200 mg/day for prophylaxis in patients &gt;60 years, 300 mg/day for prophylaxis in patients &lt;60 years and for therapy in patients &gt;60 years, and 400 mg/day for therapy in patients &lt;60 years has been proposed. At this dosing regimen, the PK/PD target for prophylaxis and therapy is reached in 95% and 90% of population, respectively, representing significantly improved outcomes in comparison with the uniform dose.

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

2023

Kód důvěrnosti údajů

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

Název periodika

Antibiotics

ISSN

2079-6382

e-ISSN

2079-6382

Svazek periodika

12

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

13

Strana od-do

1399

Kód UT WoS článku

001071176300001

EID výsledku v databázi Scopus

2-s2.0-85172195964