Clinical pharmacokinetics of phenobarbital in neonates

Demographic and clinical pharmacokinetic data collected from term and prete rm neonates who were treated with intravenous phenobarbital have been analy sed to evaluate the role of patient characteristics in pharmacokinetic para meters. Significant relationships between total body weight (TBW) or body s urface area (BSA) and volume of distribution (Vd) and total body clearance (CL) were found. Coefficients of determination were: 0.55 and 0.59 for Vd, and 0.76 and 0.72 for CL against TBW and BSA, respectively. In addition, si gnificant relationships between height of the infants and volume of distrib ution of phenobarbital and total body clearance were observed. Coefficients of determination were 0.58 for Vd and 0.56 for CL. A weaker but significan t correlation existed between gestational age and Vd or CL of phenobarbital . Coefficients of determination were 0.43 and 0.64, respectively. There was no correlation between volume of distribution per kg body weight or total body clearance per kg body weight and any patient parameter investigated. H owever, these latter pharmacokinetic parameters tended to decrease with inc reasing gestational age and height of the neonates. The results obtained we re used to develop new loading and maintenance doses for phenobarbital in n eonates based on total body weight and body surface area and based on heigh t and gestational age for cases that weight is not available. (C) 2000 Else vier Science B.V. All rights reserved.