Comparative Pharmacodynamic-Pharmacokinetic Correlation of Oral Sustained-Release Theophylline Formulation in Adult Asthmatics

Abstract

A sustained-release formulation of theophylline with an innovative release mechanism was evaluated in adult asthmatics. The pharmacodynamics and pharmacokinetic behavior of this formulation was compared with a market formulation (Theobid®). The formulations, each containing 200 mg of anhydrous theophylline, were evaluated in six male subjects, 40–55 years of age, 151–169 cm in height, 41–60 kg in weight, who were nonsmokers with moderate chronic obstructive pulmonary disease (COPD); the study was a randomized, single-dose, open, complete crossover study with an interval of 1 week. Written consent was obtained from the patients prior to the trial. Plasma samples were obtained at 0, 1, 2, 4, 6, 8, 10, and 12 hr postadministration. Pulmonary functions were simultaneously recorded using an Erich Jaeger spirometer. Plasma theophylline assays were performed using high-performance thin-layer chromatography (HPTLC). Individual bioavailability parameters were obtained using the S-Inv computer program. Pharmacodynamic-pharmacokinetic correlation was studied using the Excel 95 version 7.0 Regression Statistics program. The test formulation (innovator) was found to be comparable with the marketed product with respect to tmax, t1/2 and Kel (p <. 05). A significant difference in the means of Cmax and AUC0–12 between the innovator and the market formulation indicated a superior extent of absorption from the innovator formulation. A good pharmacodynamic-pharmacokinetic correlation was observed when plasma theophylline concentration was compared with forced expiratory volume.