Bioequivalence and pharmacokinetics of a new theophylline slow release formulation, E-0686.

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The bioavailabilities of 6 theophylline slow-release preparations (E-0686) were compared using a crossover design with 16 healthy volunteers. The formulations used were 50% granule-1 (Gra-1), 50% granule-2 (Gra-2), a 50 mg tablet (T-50), a 100mg tablet (T-100), a 200mg tablet (T-200), a 300mg tablet (T-300), and a plain, uncoated aminophylline tablet (Neophylline®, NT). In experiment I of the two, 400mg equivalent doses of theophylline in the form of Gra-1, Gra-2, T-200 and NT were administered under the fasting condition, while in experiment II, T-20, T-100, T-200, and T-300 (T-300 was 300mg instead of 400mg) were used. All the E-0686 formulations found to have equivalent bioavailability. The relative extent of bioavailability of the E-0686 formulations were 91.3-98.1%, and Cmax was significantly lower, while Tmax and MRT were prolonged, compared with the values for NT. Using % change as an index, the variation of serum concentrations after repeated administration of T-200 in experiments I and U was about 20% in the absorption phase and about 10% after the peak concentration. Since all E-0686 formulations were well described by the one compartment open model with first order absorption and showed high reproducibility of serum levels, it was suggested that optimal adjustment of dosage regimen with these formulations will be easily applicable in around-the-clock therapy.
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