KINETICS OF ABSORPTION OF A NEW ONCE-A-DAY FORMULATION OF THEOPHYLLINE IN THE PRESENCE AND ABSENCE OF FOOD

Two three-way crossover studies were done to characterize the drug rel ease characteristics of Monospan (3M Pharmaceuticals, St. Paul, MN) ca psules, a new once-a-day theophylline formulation. In the first study, 22 healthy males received single 450-mg doses of Monospan in the pres ence and absence of a high-fat breakfast; the same dose of Somophyllin (Fisons, Rochester, NY) immediate-release liquid was given to fasted subjects as a reference. The second study involved 29 healthy males gi ven a single dose of 900 mg of Monospan in the presence and absence of the same high-fat meal; Theo-24 (G. D. Searle and Co., Skokie, IL) ca psules were given to fasted subjects as a reference. The results of bo th studies showed that food did not affect the absorption of theophyll ine from Monospan; peak concentration, time to peak concentration, and area under the serum concentration-time curve were all unchanged. The absorption rates were similar with both strengths and dietary conditi ons and showed that theophylline was absorbed slowly from Monospan at a constant rate (approximately 3.2%/h) over 24 h. Absorption continued past 24 h, and the extent of absorption from Monospan compared with t hat from each reference averaged 88% or higher. A good correlation (r > 0.980) was observed for Monospan between the amount absorbed in vivo and the amount released in the in vitro dissolution test, a result th at demonstrates the precise rate control of Monospan. We conclude that Monospan is a suitable once-a-day formulation that can be taken witho ut regard to food.