Time-dependent absorption of theophylline in man

Area of Science:

• Pharmacokinetics
• Chronopharmacology
• Drug Absorption

Background:

• Theophylline is a widely used bronchodilator for respiratory diseases.
• Understanding the influence of dosing time on drug pharmacokinetics is crucial for optimizing therapy.
• Previous studies have suggested diurnal variations in drug absorption and metabolism.

Purpose of the Study:

• To investigate the impact of oral versus intravenous aminophylline administration at different times of day on theophylline plasma concentrations.
• To determine if time-dependent differences in theophylline pharmacokinetics are due to absorption, distribution, or elimination.

Main Methods:

• A pharmacokinetic study involving 16 healthy volunteers.
• Administration of oral or intravenous aminophylline (125 mg) at 9:00 A.M. and 9:00 P.M. under controlled food conditions.
• Plasma theophylline concentrations were measured over time using homogeneous enzyme immunoassay.

Main Results:

• Oral aminophylline showed significantly higher plasma concentrations 1.5 and 2 hours post-dose in the morning compared to the evening (P < 0.05).
• Morning oral doses resulted in a significantly higher mean peak plasma concentration (P < 0.05) and faster time to peak concentration (P = 0.02).
• No significant differences in elimination half-life or area under the curve were observed for oral doses, and no significant differences were found for intravenous aminophylline between morning and evening.

Conclusions:

• Time-dependent differences in theophylline pharmacokinetics following oral administration are primarily attributed to variations in gastrointestinal absorption.
• Distribution and elimination of theophylline do not appear to be significantly affected by the time of day.
• These findings suggest that the timing of oral aminophylline administration can influence its absorption and subsequent plasma concentrations.