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Theophylline pharmacokinetics in patients with bronchopulmonary dysplasia
M C Nahata1, D Serafini, R Edwards
1College of Pharmacy, Ohio State University, Columbus.
Insights
Theophylline pharmacokinetics in infants with bronchopulmonary dysplasia (BPD) show significant variability. Doses of 4-7 mg/kg/day may be needed, and serum concentration monitoring is crucial for effective BPD treatment.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Respiratory Medicine
Background:
- Theophylline is a common treatment for reducing airway resistance in infants with bronchopulmonary dysplasia (BPD).
- Limited data exists on theophylline's pharmacokinetic profile in this vulnerable patient population.
Purpose of the Study:
- To investigate the pharmacokinetics of theophylline in infants diagnosed with BPD.
- To evaluate the intrapatient variability of theophylline serum concentrations in these infants.
Main Methods:
- Nineteen infants (gestational age: 27-33 weeks; postnatal age: 12-165 days) received daily theophylline doses ranging from 2-12 mg/kg/day.
- Multiple serum theophylline concentrations were measured for each patient throughout the study period.
Main Results:
- Apparent clearance of theophylline varied between 0.28 and 0.51 ml/min/kg.
- Steady-state trough serum concentrations ranged from 3.5 to 11.2 micrograms/ml.
- Significant twofold intrapatient variability in normalized theophylline concentrations was observed.
Conclusions:
- Theophylline doses of 4-7 mg/kg/day may be necessary to achieve a target serum concentration of 10 micrograms/ml in BPD infants.
- Individualized monitoring of theophylline serum concentrations is essential for optimizing therapy in infants with BPD.
Abstract:
Theophylline is commonly used to decrease airway resistance in patients with bronchopulmonary dysplasia (BPD). Little is known, however, about theophylline's pharmacokinetics in infants' with BPD. The objectives of this study were: (i) to examine the pharmacokinetics of theophylline; and (ii) to assess the intrapatient variation in theophylline serum concentration in BPD. Nineteen patients (gestational age: 27-33 weeks, postnatal age: 12-165 days) received 2-12 mg/kg/day theophylline. Multiple serum concentrations of theophylline were determined in each patient. Apparent clearance of theophylline ranged from 0.28 to 0.51 ml/min/kg. The steady-state trough serum concentration of theophylline ranged from 3.5 to 11.2 micrograms/ml. Based on our data, theophylline doses of 4-7 mg/kg/day may be required to achieve an average steady-state serum concentration of 10 micrograms/ml. Substantial intrapatient (twofold) variability was observed in theophylline concentrations normalized for dose during therapy. The data indicate that the theophylline serum concentration should be monitored for individualizing therapy in infants with BPD.