Pharmacokinetic evaluation of two theophylline dosing methods for infants.
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)
Kraus
D M
DM
Department of Pharmacy Practice, University of Illinois at Chicago 60612.
Hatzopoulos
F K
FK
Reitz
S J
SJ
Fischer
J H
JH
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*
D013806:Theophylline