Conversion from intravenous to oral dosing using sustained-release theophylline tablets

Area of Science:

• Pharmacokinetics
• Clinical Pharmacology
• Respiratory Medicine

Background:

• Theophylline is a bronchodilator used for asthma management.
• Accurate dosing is crucial to maintain therapeutic levels and avoid toxicity.
• Individual variability in theophylline clearance necessitates personalized dosing strategies.

Purpose of the Study:

• To determine theophylline total body clearance in asthmatic patients.
• To calculate appropriate Theo-Dur dosing rates based on individual clearance.
• To evaluate the accuracy of calculated oral doses compared to intravenous administration.

Main Methods:

• Measured steady-state serum theophylline concentrations during constant-rate intravenous aminophylline infusion.
• Calculated theophylline total body clearance and Theo-Dur dosing rates.
• Administered oral Theo-Dur every 12 hours and monitored serum concentrations.
• Assessed patient compliance and theophylline toxicity.

Main Results:

• Theophylline total body clearance and dosing rates varied more than threefold among patients.
• The difference between intravenous steady-state and average oral serum concentrations was 1.2 µg/mL for similarly dosed patients.
• Peak to trough serum theophylline concentrations after the first oral dose averaged 7.8 µg/mL.
• Eight of nine compliant patients had a trough serum theophylline concentration of 10.4 µg/mL 12 hours after the last dose.

Conclusions:

• Individual theophylline clearance significantly impacts dosing requirements.
• Calculated dosing regimens can achieve therapeutic serum concentrations with careful monitoring.
• Compliance is a critical factor in successful theophylline therapy for asthma.