Affordable Access

The population pharmacokinetics of theophylline in neonates and young infants

Journal of Pharmacokinetics and Pharmacodynamics
Publication Date
  • Medicine
  • Pharmacology


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.

There are no comments yet on this publication. Be the first to share your thoughts.


Seen <100 times

More articles like this

The population pharmacokinetics of theophylline in...

on Journal of pharmacokinetics an... February 1989

Population pharmacokinetics of caffeine in neonate...

on Therapeutic drug monitoring June 1996

Population pharmacokinetics of ketorolac in neonat...

on American journal of therapeuti... 2009

Population pharmacokinetics of micafungin in neona...

on Antimicrobial Agents and Chemo... June 2010
More articles like this..