Parametric and Nonparametric Population Pharmacokinetic Models to Assess Probability of Target Attainment of Imipenem Concentrations in Critically Ill Patients

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F21%3A73612448" target="_blank" >RIV/61989592:15110/21:73612448 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709176/pdf/pharmaceutics-13-02170.pdf" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709176/pdf/pharmaceutics-13-02170.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/pharmaceutics13122170" target="_blank" >10.3390/pharmaceutics13122170</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Parametric and Nonparametric Population Pharmacokinetic Models to Assess Probability of Target Attainment of Imipenem Concentrations in Critically Ill Patients

Popis výsledku v původním jazyce

Population pharmacokinetic modeling and simulation (M&amp;S) are used to improve antibiotic dosing. Little is known about the differences in parametric and nonparametric M&amp;S. Our objectives were to compare (1) the external validation of parametric and nonparametric models of imipenem in critically ill patients and (2) the probability of target attainment (PTA) calculations using simulations of both models. The M&amp;S software used was NONMEM 7.2 (parametric) and Pmetrics 1.5.2 (nonparametric). The external predictive performance of both models was adequate for eGFRs ≥ 78 mL/min but insufficient for lower eGFRs, indicating that the models (developed using a population with eGFR ≥ 60 mL/min) could not be extrapolated to lower eGFRs. Simulations were performed for three dosing regimens and three eGFRs (90, 120, 150 mL/min). Fifty percent of the PTA results were similar for both models, while for the other 50% the nonparametric model resulted in lower MICs. This was explained by a higher estimated between-subject variability of the nonparametric model. Simulations indicated that 1000 mg q6h is suitable to reach MICs of 2 mg/L for eGFRs of 90–120 mL/min. For MICs of 4 mg/L and for higher eGFRs, dosing recommendations are missing due to largely different PTA values per model. The consequences of the different modeling approaches in clinical practice should be further investigated.

Název v anglickém jazyce

Parametric and Nonparametric Population Pharmacokinetic Models to Assess Probability of Target Attainment of Imipenem Concentrations in Critically Ill Patients

Popis výsledku anglicky

Population pharmacokinetic modeling and simulation (M&amp;S) are used to improve antibiotic dosing. Little is known about the differences in parametric and nonparametric M&amp;S. Our objectives were to compare (1) the external validation of parametric and nonparametric models of imipenem in critically ill patients and (2) the probability of target attainment (PTA) calculations using simulations of both models. The M&amp;S software used was NONMEM 7.2 (parametric) and Pmetrics 1.5.2 (nonparametric). The external predictive performance of both models was adequate for eGFRs ≥ 78 mL/min but insufficient for lower eGFRs, indicating that the models (developed using a population with eGFR ≥ 60 mL/min) could not be extrapolated to lower eGFRs. Simulations were performed for three dosing regimens and three eGFRs (90, 120, 150 mL/min). Fifty percent of the PTA results were similar for both models, while for the other 50% the nonparametric model resulted in lower MICs. This was explained by a higher estimated between-subject variability of the nonparametric model. Simulations indicated that 1000 mg q6h is suitable to reach MICs of 2 mg/L for eGFRs of 90–120 mL/min. For MICs of 4 mg/L and for higher eGFRs, dosing recommendations are missing due to largely different PTA values per model. The consequences of the different modeling approaches in clinical practice should be further investigated.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Pharmaceutics

ISSN

1999-4923

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

16

Strana od-do

2170

Kód UT WoS článku

000736547400001

EID výsledku v databázi Scopus

2-s2.0-85121420963