Bioequivalence of immediate-release theophylline capsules

A three-way crossover study in 18 healthy male volunteers was conducted to evaluate the bioequivalence of three different 200 mg anhydrous theophyllin e immediate-release (IR) capsules. The products had not. been rated as ther apeutically equivalent by the US Food and Drug Administration (FDA) owing t o a lack of bioequivalence data. Serum samples were obtained from 0 to 34 h after dosing. Mean time of maximum serum concentration (T-max) ranged from 1.3 to 1.4 h. Mean values for the maximum serum concentration (C-max) and the area under the serum concentration-time curves (AUC) differed by <5% fo r the three products. The confidence limits for Ln-transformed C-max and AU C ranged from greater than or equal to 89 to less than or equal to 113%. It was concluded that the three products were bioequivalent. in addition, the rapid in vitro dissolution of these formulations, as well as the reported high solubility and high permeability of theophylline, was predictive of th e lack of any bioavailability differences among the three products. Copyrig ht (C) 1999 John Wiley & Sons, Ltd.