title: The population pharmacokinetics of theophylline in neonates and young infants.
abstract: The population pharmacokinetics of theophylline were evaluated using 391 theophylline serum concentration measurements from 108 neonates and young infants (postnatal age 0-26 weeks), who received theophylline for the treatment of neonatal apnea. A one-compartment pharmacokinetic model with first-order elimination was used, with intravenous aminophylline and oral theophylline administration modeled as zero-order infusions. The effect of a variety of developmental and demographic factors on clearance (CL) and volume (V) were investigated. Hypothesis testing to evaluate potentially significant factors produced a final model in which clearance was based on weight (kg) raised to an exponential power and postnatal age (weeks), with CL (ml/hr) = 17.5 (weight)1.28 + 1.17 (postnatal age). Clearance was reduced by 12% for patients receiving parenteral nutrition. Volume of distribution in this population was adequately described using only weight, with V (L) = 0.858 L/kg. Bioavailability of orally administered drug was not significantly less than unity. Interindividual variability in clearance was modest, with a coefficient of variation for clearance of 16%. An estimate of interindividual variability in volume could not be obtained. As a measure of residual variability in theophylline serum concentrations, the coefficients of variation for theophylline serum concentrations of 5.0, 10.0, and 13.0 mg/L were found to be approximately, 25, 12, and 9%, respectively. The identification of influential patient factors and the quantification of their influence on theophylline disposition allow for a priori estimates of theophylline pharmacokinetic parameters in these patients.
authors.affiliation: College of Pharmacy, University of Texas, Austin 78712.
authors.forename: E S
authors.initials: ES
authors.lastname: Moore
authors.forename: R G
authors.initials: RG
authors.lastname: Faix
authors.forename: R C
authors.initials: RC
authors.lastname: Banagale
authors.forename: T H
authors.initials: TH
authors.lastname: Grasela
mesh_terms: D000375:Aging / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008954:Models, Biological; D011153:Population; D012044:Regression Analysis; D013223:Statistics as Topic; D013806:Theophylline / Q000493:pharmacokinetics*
chemical_list: D013806:Theophylline