Bioequivalence of immediate-release theophylline capsules

Area of Science:

• Pharmacokinetics and Drug Bioavailability
• Pharmaceutical Sciences
• Clinical Pharmacology

Background:

• Three 200 mg anhydrous theophylline immediate-release (IR) capsule products lacked therapeutic equivalence ratings from the US FDA due to insufficient bioequivalence data.
• Theophylline is a widely used medication, making the bioequivalence of its formulations critical for patient care.

Purpose of the Study:

• To evaluate the bioequivalence of three different 200 mg anhydrous theophylline IR capsule formulations.
• To provide necessary bioequivalence data for regulatory assessment.

Main Methods:

• A three-way crossover study design was employed involving 18 healthy male volunteers.
• Serum samples were collected over 34 hours post-dosing to determine pharmacokinetic parameters.
• Key parameters assessed included maximum serum concentration (C(max)), area under the serum concentration-time curve (AUC), and time to maximum concentration (T(max)).

Main Results:

• The mean time to maximum serum concentration (T(max)) was consistent across all three products, ranging from 1.3 to 1.4 hours.
• Mean C(max) and AUC values varied by less than 5% among the three theophylline formulations.
• Confidence intervals for Ln-transformed C(max) and AUC fell within the acceptable bioequivalence range (89% to 113%).

Conclusions:

• The three investigated 200 mg anhydrous theophylline IR capsule products demonstrated bioequivalence.
• The in vitro dissolution profiles, coupled with theophylline's known high solubility and permeability, predicted the observed lack of bioavailability differences.