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Theophylline absorption from 2 sustained-release theophylline (S-RT) formulations was examined over 2 consecutive days during continuous therapy in 8 clinically stable hospitalized patients with moderate to severe asthma. Theo-24, a formulation intended for once-daily dosing, produced larger fluctuations in serum theophylline concentration (STC) than did twice-daily Theo-Dur (214 +/- 106% versus 89 +/- 33%, p less than 0.02). Bioavailability for both formulations was essentially complete over 2 consecutive study days (95 +/- 22% and 87 +/- 8% for Theo-Dur versus 88 +/- 21% and 87 +/- 24% for Theo-24 on Days 1 and 2, respectively). The time of maximal STC (Tmax) and minimal STC (Tmin) over a 24-h period were relatively predictable for Theo-24 with Tmax 6 to 14 h postdose, and Tmin occurring at the time of dose. However, only Tmax (4 to 10 h post-A.M. dose) was predictable for Theo-Dur. The mean maximal STC over a 24-h period (Cmax) for Theo-Dur was 13.9 (range, 8.9 to 20.7 micrograms/ml), whereas the mean 6-h post-AM dose STC was 13.0 (range, 8.0 to 20.7 micrograms/ml), indicating that the STC at this 6-h time point represents a very close estimate of the true Cmax. Similarly, the mean Cmax for Theo-24 was 14.5 (range, 6.2-20.4 micrograms/ml), and the mean 10-h post-dose STC was 13.7 (range, 3.6 to 20.4 micrograms/ml), suggesting that this time point approximates the true Cmax.(ABSTRACT TRUNCATED AT 250 WORDS)
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