Circadian variation in steady-state trough theophylline concentrations

Area of Science:

• Pharmacokinetics
• Clinical Pharmacology

Background:

• Theophylline is a medication used to treat respiratory diseases.
• Steady-state pharmacokinetics are crucial for effective therapeutic drug monitoring.
• Diurnal variations in drug concentrations can impact dosing strategies.

Purpose of the Study:

• To examine the temporal variation in trough (predose) theophylline concentrations at steady state.
• To determine the significance of diurnal changes in serum theophylline levels.

Main Methods:

• Analysis of trough theophylline concentrations in adult subjects at steady state.
• Comparison of morning and evening trough concentrations.
• Repetitive studies in individuals to assess reproducibility of temporal variations.

Main Results:

• Adults generally exhibit 10-16% higher morning trough theophylline concentrations than evening trough concentrations.
• This morning-to-evening drop in theophylline levels is statistically significant.
• Significant diurnal variations (±20% to ±40%) in trough-to-trough theophylline concentrations are observed in some adults.
• Individual reproducibility in the direction of temporal variation was noted.

Conclusions:

• Temporal variation in trough theophylline concentrations is a real phenomenon, not random variability.
• Consistent daily blood sampling times are essential for accurate theophylline dosage monitoring.
• Understanding diurnal fluctuations is critical for optimizing theophylline therapy.