In a multiple-dose, two-way, crossover study with 18 healthy, normal adults, the bioavailability from Theo-Dur Sprinkle administered as intact capsules was evaluated using Theo-Dur Sustained Action Tablets as the reference products. Fifteen subjects received 400 mg at 7:00 AM and 7:00 PM while 3 subjects received 200 mg because of low theophylline clearance. All meals and snacks were provided to the subjects during the course of this study, with breakfast at 9:00 AM, lunch at 12:30 PM, a snack at 3:00 PM, and dinner at 9:00 PM. Theo-Dur Sprinkle produced mean Cmax and Cmin theophylline serum levels of 10.4 ± 2.6 and 6.9 ± 1.8 mcg/ml as compared with a Cmax and Cmin of 10.5 ± 2.8 and 7.5 ± 2.7 mcg/ml for Theo-Dur tablets. The mean percent fluctuation normalized to Css was 38.8± 8.5% for Theo-Dur Sprinkle and 33.4 ± 9.7% for Theo-Dur Tablets (% fluctuation = 100 (Cmax-Cmin)/Css, where Css = AUC_0-12/dosing interval). The mean percent fluctuation when normalized to Cmin was 51.9 ± 15.4% for Theo-Dur Sprinkle and 43.9 ± 17.4% for Theo-Dur Tablets (% fluctuation = 100 (Cmax-Cmin)/Cmin). The average peak-trough differences over 12 hours for Theo-Dur Sprinkle and Theo-Dur tablets were 3.5 ± 1.2 and 3.0 ± 0.7 mcg/ml, respectively. The AUC for Theo-Dur Sprinkle was 108.4 ± 26.0 while that for Theo-Dur tablets was 112.1 ± 32.5 mcg/hr/ml. In a separate study, Theo-Dur showed complete bioavailability when compared with an immediate-release product. This would suggest that bioavailability from Theo-Dur Sprinkle was complete and not statistically different from that of Theo-Dur Tablets.

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