Theophylline bioavailability following chronic dosing of an elixir and two solid dosage forms.

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Clinical Pharmacology

Background:

• Theophylline is a widely used bronchodilator with variable bioavailability.
• Commercial theophylline formulations often contain multiple active ingredients, potentially affecting drug disposition.

Purpose of the Study:

• To compare the bioavailability of theophylline from an elixir and two tablet formulations (I and II) under chronic dosing conditions.
• To evaluate the impact of co-administered ephedrine, hydroxyzine hydrochloride, and phenobarbital on theophylline pharmacokinetics.

Main Methods:

• Healthy volunteers received chronic dosing of theophylline elixir and two tablet formulations, compared to an acute elixir dose.
• Serum theophylline concentrations were measured over time to determine area under the curve (AUC) and elimination half-life (t 1/2).
• Statistical analyses were performed to compare pharmacokinetic parameters between treatments.

Main Results:

• Theophylline absorption (AUC) was similar across all tested formulations after correcting for elimination half-life (t 1/2).
• Chronic elixir administration resulted in a significantly higher AUC and a prolonged t 1/2 compared to acute elixir and Tablet II.
• Tablet formulations showed varying effects on t 1/2, with Tablet I having a longer t 1/2 than Tablet II and acute elixir.

Conclusions:

• The extent of theophylline absorption is comparable among the tested elixir and tablet formulations.
• Chronic theophylline elixir use may inhibit its metabolism, leading to a prolonged half-life.
• The presence of ephedrine, hydroxyzine, or phenobarbital may influence theophylline metabolism, warranting further investigation into drug interactions.