The Contin delivery system: dosing considerations.

The combination of hydrated cellulose with higher aliphatic alcohol forms the basis of the Contin delivery system, used in the development of tablet forms of sustained-release aminophylline, theophylline, morphine, and other drugs. Extensive clinical and pharmacokinetic evaluation of Uniphyl (anhydrous theophylline) tablets, 400 mg, shows that once-daily morning dosing is at least equivalent to twice-daily administration of theophylline. Ingestion of the once-daily product with a high-calorie-high-fat meal in volunteers increased the absorption of theophylline without accompanying "dose-dumping." Extensive pharmacokinetic evaluation in patients with food intake not controlled has yielded bioavailability comparable to that of twice-daily theophylline. Ongoing research suggests that evening administration of Uniphyl tablets may represent a rational dosing schedule for patients with asthma who often exhibit increased bronchoconstriction in the morning. In these studies patients demonstrate improved pulmonary function in the morning compared with use of twice-daily theophylline when once-daily Uniphyl is administered in the evening. Thus, evening administration of once-daily theophylline may block the morning dip in lung function commonly seen.