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Pharmacokinetics of theophylline in infants with bronchiolitis
Insights
Theophylline clearance is substantially lower and half-life longer in infants with bronchiolitis compared to older children. Monitoring theophylline serum concentrations is crucial due to significant clearance variability and potential toxicity risks.
Area of Science:
- Pharmacokinetics
- Pediatric Pharmacology
- Respiratory Medicine
Background:
- Theophylline is a common medication for respiratory conditions in infants.
- Bronchiolitis is a frequent cause of infant hospitalization, often treated with theophylline.
- Understanding theophylline pharmacokinetics in this population is essential for safe and effective dosing.
Purpose of the Study:
- To investigate the pharmacokinetic profile of theophylline in infants diagnosed with bronchiolitis.
- To compare theophylline clearance and half-life in infants with published data from older children.
- To assess the variability in theophylline pharmacokinetics and its implications for therapeutic drug monitoring.
Main Methods:
- A pharmacokinetic study involving 12 infants (3 weeks to 6.5 months) with bronchiolitis.
- Administration of single or multiple intravenous doses of aminophylline.
- Measurement of serum and urine theophylline concentrations using High-Performance Liquid Chromatography (HPLC).
Main Results:
- Theophylline clearance was significantly lower and half-life longer in infants compared to children over one year of age.
- A five-fold variation in theophylline clearance was observed among the study participants.
- Peak serum theophylline concentrations ranged from 8.48-21.6 µg/ml.
- Total, renal, and non-renal clearance values were determined, along with apparent volume of distribution and elimination half-life.
Conclusions:
- Infants with bronchiolitis exhibit distinct theophylline pharmacokinetic parameters, necessitating careful dosing.
- The considerable inter-individual variability in theophylline clearance highlights the importance of therapeutic drug monitoring.
- Monitoring serum theophylline levels can help mitigate the risk of adverse events and optimize treatment efficacy in this vulnerable population.
Abstract:
Theophylline pharmacokinetics were studied in 12 infants (age 3 weeks-6.5 months) with bronchiolitis. 9 of the 12 patients received a single dose of aminophylline (5.0-8.5 mg/kg) whereas the remainder were at steady-state receiving multiple doses (2.5-5.0 mg/kg) of aminophylline. The dose was administered IV over 0.5-1.0 h. An HPLC method was used to measure theophylline concentrations in serum and urine. Peak serum concentrations of theophylline measured by HPLC ranged from 8.48-21.6 micrograms/ml. Total, renal and nonrenal clearance of theophylline ranged from 4.66 to 19.25, 1.07 to 5.76 and 3.59 to 16.83 ml/min/m2, respectively. Mean apparent volume of distribution and elimination half-life were 8.75 l/m2 and 11.38 h, respectively. Although no significant correlation was observed between age and theophylline kinetic parameters, clearance appeared to increase and half-life decrease with age. Our patients had a substantially lower clearance and longer half-life as compared to published data in children greater than 1 year of age. A five-fold variation in theophylline clearance demonstrates the need for monitoring theophylline serum concentration to minimize the risk of potential toxicity.