Population pharmacokinetics of levetiracetam in neonates with seizures.

Abstract:

WHAT IS KNOWN AND OBJECTIVE:This study developed a population pharmacokinetic (PK) model of levetiracetam (LEV) for treating neonatal seizures (NS) and determined the influence of clinically relevant covariates to explain the interindividual variability and residual error. METHODS:Twenty newborns admitted to the Neonatal Intensive Care Unit at the Hospital Central "Dr. Ignacio Morones Prieto" were included. LEV doses were administered by intermittent infusion. Blood samples were drawn 3 times post-infusion. Levetiracetam was quantified by a chromatographic technique. NONMEM software was used to determine the population PK model of LEV in neonates and the influence of clinical covariates on drug disposition. RESULTS AND DISCUSSION:The LEV PK in neonates is described by a one-compartment open model with first-order elimination. The influence of creatinine clearance (CRCL) and body weight (BW) on clearance (CL[L/h] = 0.47*CRCL), as well as the volume of the distribution (Vd[L] = 0.65*BW) of LEV, were confirmed, considering interindividual variabilities of 36% and 22%, respectively, and a residual error of 13%. WHAT IS NEW AND CONCLUSION:Based on the PK of LEV in neonates and the influence of the final PK model, a priori dosing guidelines are proposed considering CRCL, BW and LEV plasma concentrations between 6 and 20 mg/L for NS treatment.

journal_name

J Clin Pharm Ther

authors

Lima-Rogel V,López-López EJ,Medellín-Garibay SE,Gómez-Ruiz LM,Romero-Méndez C,Milán-Segovia RC,Romano-Moreno S

doi

10.1111/jcpt.12658

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

422-429

issue

3

eissn

0269-4727

issn

1365-2710

journal_volume

43

pub_type

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