Amélie Marsot (1), Renaud Vialet (2), Audrey Boulamery (1), Bernard Bruguerolle (1), Nicolas Simon (1)
(1) Laboratoire de Pharmacologie Médicale et Clinique APHM, Université de la Méditerranée, Marseille, France; (2) Département Réanimation Pédiatrique, Hôpital Nord, Marseille, France.
Objectives: Phenobarbital is widely used for treatment of neonatal seizures and the prevention of neonatal hyperbilirubinaemia. A pharmacokinetic model of phenobarbital in 35 neonates and infants was described in 2005 by Yukawa et al., studying oral and rectal routes. A new model in a similar population is proposed for intravenous administration.
Methods: 27 neonates and infants (weight: 1.2-10.0 kg; PNA: 0-466 days) hospitalized in a pediatric intensive care unit, were studied. Total mean dose of 194 mg (40-450mg) was administered by 30-min infusion. Blood phenobarbital concentrations were determined by immunoassay method. Pharmacokinetic analysis was performed by using a non linear mixed-effect population model. Data analysing included calculation of performance error (PE), median performance error (MDPE) and median absolute performance error (MDAPE). A bootstrap was used as internal validation.
Results: Data were modelled with an allometric pharmacokinetic model using three-fourths scaling exponent for clearance and parameters. This one-compartment model gave the following results. The population typical mean (percent relative standard error (%RSE)) values for clearance (CL) and apparent volume of distribution (Vd) were 8.70 mL/H/kg (10.4%) and 1.44 L/kg (15.1%), respectively. The interindividual variability of Vd (%RSE) and intraindividual variability (%RSE) were 60% (25.0%) and 42% (27.9%), respectively. The indicators of predictive performance gave the following results: MDPE (range) was -9.5% (-74.4 to 131.7%) and MDAPE (range) was 30.1% (3.9 to 131.7%).
Conclusions: The pharmacokinetic parameters of intravenous phenobarbital in neonates and infants were estimated. The predictive performance was acceptable with a small bias. These intermediate results should be confirmed by the inclusion of new patients.
References:
[1] Yukawa et al. Journal of Clinical Pharmacy and Therapeutics 2005; 30: 159-163.
Reference: PAGE 20 (2011) Abstr 1996 [www.page-meeting.org/?abstract=1996]
Poster: Paediatrics