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The population pharmacokinetics of theophylline in neonates and young infants

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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.

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Authors and Affiliations

  1. College of Pharmacy, The University of Texas at Austin, 78712, Austin, Texas

    Emory S. Moore

  2. Department of Pediatrics-Newborn Services, The University of Michigan Medical Center, 48109, Ann Arbor, Michigan

    Roger G. Faix

  3. Apnea and SIDS Program, Emanuel Hospital and Health Center, 97227, Portland, Oregon

    Raul C. Banagale

  4. Pharmacoepidemiology Research Center, State University of New York at Buffalo, Schools of Pharmacy and Medicine, Amherst, New York

    Thaddeus H. Grasela

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  1. Emory S. Moore
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  2. Roger G. Faix
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  4. Thaddeus H. Grasela
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Additional information

This project was supported in part by a National Institutes of Health General Research Center grant 5MOI-RR00042.

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Moore, E.S., Faix, R.G., Banagale, R.C. et al. The population pharmacokinetics of theophylline in neonates and young infants. Journal of Pharmacokinetics and Biopharmaceutics 17, 47–66 (1989). https://doi.org/10.1007/BF01059087

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  • DOI: https://doi.org/10.1007/BF01059087

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