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Pharmacokinetics and dose regimen of oral theophylline in children
Insights
Theophylline absorption is rapid and complete in children. Younger children (2-8 years) eliminate theophylline faster than older children (9-16 years), requiring dose adjustments for optimal therapeutic drug monitoring.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Clinical Pharmacy
Background:
- Theophylline is a bronchodilator used in managing respiratory conditions in children.
- Understanding theophylline pharmacokinetics is crucial for effective dosing and minimizing adverse effects.
Purpose of the Study:
- To determine the pharmacokinetics of oral theophylline (tablets and solution) in children aged 0.6-16 years.
- To compare theophylline elimination between younger and older children.
- To assess adverse effects of oral theophylline solution.
Main Methods:
- Oral administration of theophylline in tablet (Oxyphyllin) and solution (Teovent) forms to 22 children.
- Intravenous administration in 4 children.
- Pharmacokinetic parameter determination (half-time, clearance).
- Adverse event monitoring in 19 additional children.
Main Results:
- Rapid and near-complete absorption of theophylline from both oral formulations (mean half-time 14.3-16.1 min).
- Younger children (2-8 years) exhibited significantly shorter elimination half-time and higher plasma clearance compared to older children (9-16 years).
- Gastrointestinal disturbances were common but generally not severe; taste led to discontinuation in two cases.
Conclusions:
- Theophylline pharmacokinetics vary significantly with age in children, necessitating age-specific dosing strategies.
- Simulations suggest specific dosing regimens for different age groups to maintain therapeutic theophylline plasma levels (10-20 µg/mL).
- Individual dose titration is essential for safe and effective theophylline therapy in pediatric patients.
Abstract:
The pharmacokinetics of theophylline after oral administration in tablet (Oxyphyllin) or solution (Teovent) form was determined in 22 children 0.6-16 years of age. Four of these children also received intravenous theophylline. The absorption of theophylline both from the tablets and from the solution was rapid (mean half-time 14.3 and 16.1 min., respectively) and almost complete. The youngest children (2-8 years) given tablets had a significantly shorter half-time of elimination and a higher total plasma clearance than children aged 9-16 years. Adverse effects during treatment with the oral solution were studied in another 19 children. Medication was stopped by the parents of two children because of the unpleasant taste. Gastrointestinal disturbances were frequent but not serious enough to cause discontinuation of treatment. Simulations based on obtained pharmacokinetic data showed that in the average child below nine years of age oral theophylline, 6-8 mg/kg three times daily, would give plasma levels between 10 and 20 micrograms/ml (55-110 mumol/l) for about 60-70% of the day. A dose of 6 mg/kg four times daily would achieve such concentrations during almost 24 hrs of the day. In the average child aged 9-16 years a reduced dose of about 5-6 mg/kg three times daily would suffice to produce plasma levels of 10-20 micrograms/ml owing to the slower elimination of the drug in this age group. Individual titration of the dose is necessary for optimal treatment with theophylline in all age groups.