title: Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach.
abstract: Phenobarbital is widely used for treatment of neonatal seizures. Its optimal use in neonates and young infants requires information regarding pharmacokinetics. The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated. Routine clinical pharmacokinetic data were retrospectively collected from 48 neonates and infants (weight: 0.7-10 kg; patient's postnatal age: 0-206 days; GA: 27-42 weeks) treated with phenobarbital, who were administered as intravenous or suspension by oral routes and hospitalized in a paediatric intensive care unit. Total mean dose of 4.6 mg/kg (3.1-10.6 mg/kg) per day was administered by 30-min infusion or by oral route. Pharmacokinetic analysis was performed using a nonlinear mixed-effect population model software). Data were modelled with an allometric pharmacokinetic model, using three-fourths scaling exponent for clearance (CL). The population typical mean [per cent relative standard error (%RSE)] values for CL, apparent volume of distribution (Vd ) and bioavailability (F) were 0.0054 L/H/kg (7%), 0.64 L/kg (15%) and 48.9% (22%), respectively. The interindividual variability of CL, Vd , F (%RSE) and residual variability (%RSE) was 17% (31%), 50% (27%), 39% (27%) and 7.2 mg/L (29%), respectively. The absolute bioavailability of phenobarbital in neonates and infants was estimated. The dose should be increased when switching from intravenous to oral administration.
authors.affiliation: Service de Pharmacologie Médicale et Clinique, hôpital Timone, bat F, 264 Rue, Saint Pierre, 13385, Marseille Cedex 5, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Marsot
authors.forename: Véronique
authors.initials: V
authors.lastname: Brevaut-Malaty
authors.forename: Renaud
authors.initials: R
authors.lastname: Vialet
authors.forename: Audrey
authors.initials: A
authors.lastname: Boulamery
authors.forename: Bernard
authors.initials: B
authors.lastname: Bruguerolle
authors.forename: Nicolas
authors.initials: N
authors.lastname: Simon
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D001682:Biological Availability; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010634:Phenobarbital / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D014018:Tissue Distribution
chemical_list: D000927:Anticonvulsants; D010634:Phenobarbital
keywords: absolute bioavailability; paediatrics; pharmacokinetic; phenobarbital