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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

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

Publication year

2021

Confidentiality

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

Name of the periodical

Pharmaceutics

ISSN

1999-4923

e-ISSN

—

Volume of the periodical

13

Issue of the periodical within the volume

12

Country of publishing house

CH - SWITZERLAND

Number of pages

16

Pages from-to

2170

UT code for WoS article

000736547400001

EID of the result in the Scopus database

2-s2.0-85121420963