Related Experiment Videos
Pharmacokinetic evaluation of two theophylline dosing methods for infants
D M Kraus1, F K Hatzopoulos, S J Reitz
1Department of Pharmacy Practice, University of Illinois at Chicago 60612.
Insights
Current theophylline dosing guidelines for infants show significant variability in serum concentrations. Both postnatal age (PNA) and FDA dosing methods result in potentially toxic or subtherapeutic levels, particularly in younger infants.
Area of Science:
- Pediatric Pharmacology
- Neonatal Therapeutics
- Clinical Pharmacy
Background:
- Theophylline is a common medication for infants.
- Limited data exist on serum concentrations from current dosing guidelines.
- Infant dosing requires careful consideration due to developmental changes.
Purpose of the Study:
- To evaluate theophylline serum concentrations using two dosing regimens in infants.
- To compare a postnatal age (PNA) equation with Federal Drug Administration (FDA) guidelines.
- To identify potential issues with current theophylline dosing in neonates and infants.
Main Methods:
- Retrospective analysis of theophylline dosing regimens.
- Evaluation in infants with known theophylline clearances (postconceptional age 31-96 weeks).
- Comparison of projected steady-state serum concentrations (Css) between PNA and FDA methods.
Main Results:
- Large variations in theophylline Css were observed for both regimens.
- PNA equation resulted in a mean Css of 17.7 +/- 7.6 mcg/ml; FDA guidelines yielded 5.6 +/- 2.9 mcg/ml.
- Over 40% of infants had Css < 5 mcg/ml with FDA guidelines, while over one-third had Css > 20 mcg/ml with the PNA equation.
Conclusions:
- Current theophylline dosing guidelines for infants lead to frequent toxic or subtherapeutic serum concentrations.
- The PNA equation and FDA guidelines demonstrate age-related biases in predicted Css.
- Revised dosing strategies are needed to optimize theophylline therapy in 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)