title: Pharmacokinetic evaluation of two theophylline dosing methods for infants.
abstract: Theophylline is often used in infants, yet few studies have evaluated the serum concentrations achieved with currently recommended dosing guidelines. Two theophylline dosing regimens, a postnatal age (PNA) equation and the Federal Drug Administration (FDA) dosing guidelines, were retrospectively evaluated in a group of infants, postconceptional age (PCA) 31-96 weeks, with known theophylline clearances. Large variations in theophylline concentrations were observed for both dosing regimens. Mean +/- SD projected steady-state theophylline serum concentrations, Css, were 17.7 +/- 7.6 micrograms/ml with the PNA equation (n = 40) and 5.6 +/- 2.9 micrograms/ml with the FDA guidelines (n = 52). Over one-third of Css with the PNA equation were > 20 micrograms/ml. Using the FDA guidelines, 40% of Css were < 5 micrograms/ml. The majority of infants < 40 weeks PCA attained projected Css > 20 micrograms/ml (21.7 +/- 5.1 micrograms/ml) with the PNA equation, but < 5 micrograms/ml (4.3 +/- 1.4 micrograms/ml) with FDA guidelines. An age-related bias was also observed for each dosing method. For the PNA equation, projected Css were significantly higher in infants < 40 weeks versus > or = 40 weeks PCA (21.7 +/- 5.1 versus 15.8 +/- 7.9 micrograms/ml, p < 0.01). For FDA guidelines, projected Css were significantly lower in infants < 40 weeks PCA versus older infants (4.3 +/- 1.4 versus 8.5 +/- 4.3 micrograms/ml, p < 0.001). Clinical application of currently accepted theophylline dosing guidelines for infants results in a high frequency of Css, which are potentially toxic or subtherapeutic.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago 60612.
authors.forename: D M
authors.initials: DM
authors.lastname: Kraus
authors.forename: F K
authors.initials: FK
authors.lastname: Hatzopoulos
authors.forename: S J
authors.initials: SJ
authors.lastname: Reitz
authors.forename: J H
authors.initials: JH
authors.lastname: Fischer
mesh_terms: D000375:Aging / Q000378:metabolism; D001682:Biological Availability; D005069:Evaluation Studies as Topic; D006801:Humans; D007223:Infant; D012189:Retrospective Studies; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D013806:Theophylline