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

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...

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Main Authors: Idoia Bilbao-Meseguer (Author), Helena Barrasa (Author), Eduardo Asín-Prieto (Author), Ana Alarcia-Lacalle (Author), Alicia Rodríguez-Gascón (Author), Javier Maynar (Author), José Ángel Sánchez-Izquierdo (Author), Goiatz Balziskueta (Author), María Sánchez-Bayton Griffith (Author), Nerea Quilez Trasobares (Author), María Ángeles Solinís (Author), Arantxa Isla (Author)
Format: Book
Published: MDPI AG, 2021-10-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Idoia Bilbao-Meseguer  |e author 
700 1 0 |a Helena Barrasa  |e author 
700 1 0 |a Eduardo Asín-Prieto  |e author 
700 1 0 |a Ana Alarcia-Lacalle  |e author 
700 1 0 |a Alicia Rodríguez-Gascón  |e author 
700 1 0 |a Javier Maynar  |e author 
700 1 0 |a José Ángel Sánchez-Izquierdo  |e author 
700 1 0 |a Goiatz Balziskueta  |e author 
700 1 0 |a María Sánchez-Bayton Griffith  |e author 
700 1 0 |a Nerea Quilez Trasobares  |e author 
700 1 0 |a María Ángeles Solinís  |e author 
700 1 0 |a Arantxa Isla  |e author 
245 0 0 |a Population Pharmacokinetics of Levetiracetam and Dosing Evaluation in Critically Ill Patients with Normal or Augmented Renal Function 
260 |b MDPI AG,   |c 2021-10-01T00:00:00Z. 
500 |a 10.3390/pharmaceutics13101690 
500 |a 1999-4923 
520 |a 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. 
546 |a EN 
690 |a levetiracetam 
690 |a augmented renal clearance 
690 |a intensive care 
690 |a critically ill patients 
690 |a population pharmacokinetic 
690 |a modelling 
690 |a Pharmacy and materia medica 
690 |a RS1-441 
655 7 |a article  |2 local 
786 0 |n Pharmaceutics, Vol 13, Iss 10, p 1690 (2021) 
787 0 |n https://www.mdpi.com/1999-4923/13/10/1690 
787 0 |n https://doaj.org/toc/1999-4923 
856 4 1 |u https://doaj.org/article/14f21efc86af4fcf81a42c7ab4b84e1c  |z Connect to this object online.