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Scientific article
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English

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

Published inPharmaceutics, vol. 13, no. 12, 2170
Publication date2021-12-16
First online date2021-12-16
Abstract

Population pharmacokinetic modeling and simulation (M&S) are used to improve antibiotic dosing. Little is known about the differences in parametric and nonparametric M&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&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.

eng
Keywords
  • Imipenem
  • Nonparametric
  • Parametric
  • Population pharmacokinetic modeling
  • Simulations
Funding
  • University Hospital of Geneva - [PRD 09-II-025]
  • Palacký University, Olomouc - [IGA UPOL2014 LF 008]
  • AIDA - [Health-F3-2011-278348]
  • European Commission - Combatting Bacterial Resistance in Europe [115523]
Citation (ISO format)
DE VELDE, Femke et al. Parametric and Nonparametric Population Pharmacokinetic Models to Assess Probability of Target Attainment of Imipenem Concentrations in Critically Ill Patients. In: Pharmaceutics, 2021, vol. 13, n° 12, p. 2170. doi: 10.3390/pharmaceutics13122170
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Identifiers
ISSN of the journal1999-4923
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Technical informations

Creation02/28/2022 2:07:00 PM
First validation02/28/2022 2:07:00 PM
Update time03/16/2023 6:28:10 AM
Status update03/16/2023 6:28:08 AM
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