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[Theophylline in childhood asthma. Pharmacokinetic and clinical study (author's transl)]
Insights
This study investigated the pharmacokinetics of anhydrous theophylline in children with asthma. Results showed variable absorption and dose requirements, suggesting careful monitoring is needed for effective treatment.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Respiratory Medicine
Context:
- Theophylline is a bronchodilator used for asthma management.
- Understanding its pharmacokinetics in children is crucial for optimizing therapy.
- Previous studies may not fully capture the variability in pediatric patients.
Purpose:
- To evaluate the pharmacokinetic profile of anhydrous theophylline in pediatric asthma patients.
- To assess the absorption, distribution, and clearance of theophylline via different administration routes.
- To determine the required dosage range for maintaining therapeutic plasma levels and correlate it with clinical outcomes.
Summary:
- Intravenous anhydrous theophylline exhibited a half-life of 6.06 hours, distribution volume of 0.585 L/kg, and clearance of 0.078 L/kg/w.
- Syrup formulation showed consistent, rapid, and complete absorption, reaching 11.39 mg/L at 2 hours post-dose.
- Tablet absorption was irregular, and prolonged treatment revealed a wide dose variation (10-22.5 mg/kg/day) needed to maintain therapeutic levels (10-20 mg/L).
- Correlation between actual and calculated theophylline needs was poor, with a lower proportion of good clinical results compared to literature.
Impact:
- Highlights the significant inter-individual variability in theophylline pharmacokinetics and response in children.
- Suggests that standard dosing guidelines may require adjustment based on individual patient factors.
- Emphasizes the need for therapeutic drug monitoring to ensure efficacy and safety in pediatric asthma management.
Abstract:
After an intra-venous injection of a single dose (4.24 +/- 0.94 mg/kg) of anhydrous theophylline in 20 children aged 4 to 16 years, the pharmacokinetic characteristics (mean and standard deviation) were as follow: half life (T 1/2 6.06 +/- 2.53; apparent distribution volume (Vd) 0.585 +/- 0.148 l/kg and clearance from the body (Cl) at 0.078 +/- 0.35 l/kg/w. The absorption of anhydrous theophylline syrup, given to 13 children during an exacerbation of their asthma, was consistent, quick and complete. Two hours after a dose of 6 mg/kg, the plasma levels were 11.39 +/- 2.04 mg/litre. On seven occasions, the clinical results were good. The absorption of the tablet form of anhydrous theophylline was more irregular. A prolonged course of treatment in 20 subjects aged 4.5 to 17.2 years confirmed the wide variety of doses required to maintain plasma theophylline levels in the 10 to 20 mg/litre range. The doses required varied from 10 to 22.5 mg/kg/day. The correlation between the actual and calculated needs on the basis of theophylline clearance was poor (due to the bioavailability of the drug and the close dependent character of the clearance). Seven times, the results were good (twice mean theophylline levels below 10 mg/litre). The proposition of good results in this study is less than that reported in the literature.