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Sustained-release formulations of theophylline as well as of other drugs are designed to effect a delayed but constant release of the active principle in the gastrointestinal tract, thus ensuring more prolonged blood level curves. This study was made to assess the bioavailability of two sustained-release microencapsulated formulations and one sustained-release Diffucaps formulation, in comparison with an equivalent dose of theophylline solution. As regards bioavailability, none of the three formulations differed significantly from the reference formulation. The blood levels at steady state were estimated on the basis of data obtained after a single-dose study. All three sustained release formulations showed good results after prolonged administration in terms of peaks and troughs. The time duration at which the theophylline plasma levels remain higher than 75% of the maximum steady-state levels, following 12-h dosing interval, was evaluated: for the sustained-release microencapsulated formulations this time duration reaches 100% of the dosing interval. A multiple-dose administration of the sustained-release formulations used in this study should guarantee almost complete time coverage, with blood levels sharply exceeding the minimum threshold level of the theophylline therapeutic range.

The absolute bioavailability of dihydroquinidine chloride (normal tablet and sustained-release capsule) was studied in 12 hospitalized patients with heart disease. A 300-mg dose of dihydroquinidine gluconate was administered to each patient by short intravenous infusion. After a single dose of two tablets of dihydroquinidine chloride (300 mg), the average peak concentration was 0.74 +/- 0.43 mg/l (+/- SD); following administration two capsules of the sustained-release form (500 mg dihydroquinidine chloride) the average peak concentration was 0.55 +/- 0.25 mg/l. Tmax was approximately 5 h with the dihydroquinidine tablet and 7 h with the dihydroquinidine capsule. The mean absolute bioavailability was 89 +/- 9% for the conventional tablet and 52 +/- 15% for the sustained-release capsule. After intravenous infusion of dihydroquinidine (2.63 +/- 0.29 mg/kg), the disposition of the drug is described by a two-compartment open model. The volume of distribution (Vd) was 4.67 l/kg. Distribution (t1/2 alpha = 18.63 +/- 15.2 h) and the apparent elimination half-life (t1/2 beta = 10.8 +/- 4.7 h) were longer than the corresponding values reported by Ueda et al. [1976]. These discrepancies are presumably due to the different sampling period that was extended to 24 h in our study, consequently evidencing a slower rate of elimination from 12 to 24 h. Mean total body clearance (Cl) was 0.28 +/- 0.057 l/h/kg. Urine sample collection for 48 h showed 21% of the dose was excreted unchanged. The renal clearance (Clr) was 0.062 +/- 0.018 l/h/kg.