Population pharmacokinetics of levetiracetam in neonates with seizures.
J Clin Pharm Ther
; 43(3): 422-429, 2018 Jun.
Article
en En
| MEDLINE
| ID: mdl-29265480
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 ANDDISCUSSION:
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 ANDCONCLUSION:
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piracetam
/
Convulsiones
/
Modelos Biológicos
/
Anticonvulsivantes
Tipo de estudio:
Guideline
/
Observational_studies
/
Qualitative_research
Límite:
Female
/
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
J Clin Pharm Ther
Asunto de la revista:
FARMACIA
/
TERAPEUTICA
Año:
2018
Tipo del documento:
Article