Comparison of methods for determining unbound theophylline concentrations

Area of Science:

• Pharmacokinetics
• Clinical Chemistry

Background:

• Theophylline is a medication used to treat respiratory diseases.
• Accurate monitoring of theophylline concentrations is crucial for therapeutic efficacy and safety.
• Non-invasive methods for drug monitoring are desirable.

Purpose of the Study:

• To evaluate the suitability of using tear and saliva samples to estimate theophylline concentrations.
• To compare tear and saliva theophylline levels with plasma concentrations.

Main Methods:

• Simultaneous plasma, tear, and saliva samples were collected from 22 adult male patients taking theophylline.
• Unbound theophylline concentrations were determined using equilibrium dialysis for nine subjects.
• Correlations between tear/saliva and plasma/unbound theophylline concentrations were analyzed.

Main Results:

• Tear and saliva theophylline concentrations showed positive correlations with plasma concentrations (r=0.94 for tears, r=0.84 for saliva).
• Mean tear/unbound and saliva/unbound ratios were 0.94 and 1.25, respectively.
• Saliva and tears predicted unbound theophylline concentrations within 1 microgram/ml in 78% and 50% of cases, respectively.

Conclusions:

• Saliva and tears have limited clinical utility for accurately estimating unbound theophylline concentrations.
• While correlated, these alternative matrices are not sufficiently precise for routine therapeutic drug monitoring of theophylline.