Do saliva concentrations predict plasma unbound theophylline concentrations? A problem re-examined

Area of Science:

• Pharmacokinetics
• Therapeutic Drug Monitoring

Background:

• Plasma unbound drug concentrations are considered therapeutically active.
• Theophylline is commonly prescribed for asthma and chronic bronchitis.
• Accurate monitoring of theophylline levels is crucial for effective treatment.

Purpose of the Study:

• To evaluate the utility of saliva theophylline concentrations in predicting plasma unbound theophylline levels.
• To compare stimulated and non-stimulated saliva for predicting plasma unbound theophylline.
• To assess the feasibility of using saliva for routine theophylline therapy monitoring.

Main Methods:

• 25 adult patients receiving theophylline for asthma or chronic bronchitis were studied.
• Plasma samples were ultrafiltered to determine unbound theophylline concentrations.
• Saliva samples (stimulated and non-stimulated) were collected and analyzed for theophylline concentrations.

Main Results:

• Plasma unbound theophylline concentrations showed significant correlation with total plasma (r=0.97) and stimulated saliva (r=0.973).
• Stimulated saliva (S) demonstrated a strong ability to predict unbound theophylline (F) concentrations with a mean ratio of 0.7297.
• In 92% of patients, predicted unbound theophylline concentrations from saliva were within +/- 1 microgram/ml of measured values.

Conclusions:

• Stimulated saliva is a reliable predictor of plasma unbound theophylline concentrations.
• Saliva drug monitoring offers a practical and accurate alternative for routine theophylline therapy management.
• The use of stimulated saliva samples is advocated for optimizing theophylline dose adjustments.