Population Pharmacokinetics of Levetiracetam and Dosing Evaluation in Critically Ill Patients with Normal or Augmented Renal Function.

Autor:	Bilbao-Meseguer I; Department of Pharmacy, Cruces University Hospital, Plaza de Cruces 12, 48903 Barakaldo, Spain.; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain., Barrasa H; Instituto de Investigación Sanitaria Bioaraba, 01009 Vitoria-Gasteiz, Spain.; Intensive Care Unit, Araba University Hospital, Osakidetza Basque Health Service, 01009 Vitoria-Gasteiz, Spain., Asín-Prieto E; Inserm U1070: Pharmacologie des Anti-Infectieux, Pôle Biologie Santé, Université de Poitiers, Bâtiment B36, 1 Rue Georges Bonnet, 86022 Poitiers, France., Alarcia-Lacalle A; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.; Instituto de Investigación Sanitaria Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, 01006 Vitoria-Gasteiz, Spain., Rodríguez-Gascón A; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.; Instituto de Investigación Sanitaria Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, 01006 Vitoria-Gasteiz, Spain., Maynar J; Instituto de Investigación Sanitaria Bioaraba, 01009 Vitoria-Gasteiz, Spain.; Intensive Care Unit, Araba University Hospital, Osakidetza Basque Health Service, 01009 Vitoria-Gasteiz, Spain., Sánchez-Izquierdo JÁ; Intensive Care Unit, Doce de Octubre Hospital, Avda de Córdoba, s/n, 28041 Madrid, Spain., Balziskueta G; Instituto de Investigación Sanitaria Bioaraba, 01009 Vitoria-Gasteiz, Spain.; Intensive Care Unit, Araba University Hospital, Osakidetza Basque Health Service, 01009 Vitoria-Gasteiz, Spain., Griffith MS; Intensive Care Unit, Doce de Octubre Hospital, Avda de Córdoba, s/n, 28041 Madrid, Spain., Quilez Trasobares N; Intensive Care Unit, Doce de Octubre Hospital, Avda de Córdoba, s/n, 28041 Madrid, Spain., Solinís MÁ; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.; Instituto de Investigación Sanitaria Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, 01006 Vitoria-Gasteiz, Spain., Isla A; Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.; Instituto de Investigación Sanitaria Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, 01006 Vitoria-Gasteiz, Spain.
Jazyk:	angličtina
Zdroj:	Pharmaceutics [Pharmaceutics] 2021 Oct 15; Vol. 13 (10). Date of Electronic Publication: 2021 Oct 15.
DOI:	10.3390/pharmaceutics13101690
Abstrakt:	Levetiracetam is a broad-spectrum antiepileptic drug commonly used in intensive care units (ICUs). The objective of this study is to evaluate the adequacy of levetiracetam dosing in patients with normal or augmented renal clearance (ARC) admitted to the ICU by population modelling and simulation. A multicentre prospective study including twenty-seven critically ill patients with urinary creatinine clearance (CrCl) > 50 mL/min and treated with levetiracetam was developed. Levetiracetam plasma concentrations were best described by a two-compartment model. The parameter estimates and relative standard errors (%) were clearance (CL) 3.5 L/h (9%), central volume of distribution (V1) 20.7 L (18%), intercompartmental clearance 31.9 L/h (22%), and peripheral volume of distribution 33.5 L (13%). Interindividual variability estimates were, for the CL, 32.7% (21%) and, for V1, 56.1% (29%). The CrCl showed significant influence over CL. Simulations showed that the administration of at least 500 mg every 8 h or 1000 mg every 12 h are needed in patients with normal renal function. Higher doses (1500 or 2000 mg, every 8 h) are needed in patients with ARC. Critically ill patients with normal or ARC treated with levetiracetam could be at high risk of being underdosed.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text ve formátu PDF