Computer-simulated conversion from intravenous to sustained-release oral theophylline

Area of Science:

• Pharmacokinetics and Drug Dosing
• Clinical Pharmacology
• Therapeutic Drug Monitoring

Background:

• Continuous intravenous aminophylline is used for theophylline therapy.
• Switching to oral sustained-release theophylline (Theo-Dur) requires careful timing.
• Patient factors like smoking and cirrhosis affect drug metabolism.

Purpose of the Study:

• To determine the optimal timing for the first oral theophylline dose after intravenous aminophylline discontinuation.
• To evaluate conversion strategies using pharmacokinetic simulations.
• To assess potential toxicity risks associated with current dosing recommendations.

Main Methods:

• Computer simulation using a pharmacokinetic program.
• Modeling four different oral dose administration times relative to IV infusion cessation.
• Simulations conducted in virtual patient groups: smokers, non-smokers, and those with cirrhosis.

Main Results:

• Administering the first oral dose immediately upon IV infusion discontinuation generally resulted in minimal deviation from steady-state levels.
• The timing of the first oral dose had varying impacts depending on patient group (smokers, non-smokers, cirrhosis).
• The simulated immediate conversion strategy proved effective across different patient profiles.

Conclusions:

• Immediate oral theophylline dosing upon IV aminophylline cessation is a viable conversion strategy.
• The current FDA-recommended 12-hour maintenance dose for Theo-Dur may lead to toxicity in specific patient populations.
• Pharmacokinetic modeling aids in optimizing drug conversion protocols and identifying potential dosing risks.