Once daily theophylline: multiple-dose comparison of an encapsulated micro-osmotic system (Euphylong) with a tablet (Uniphyllin).

Abstract

In a randomized, multiple-dose, cross-over study, serum theophylline concentrations (STC) were compared in 12 healthy volunteers for 24 hours after the first and seventh administration of two sustained-release formulations. The preparations tested were the new encapsulated micro-osmotic system Euphylong (E) and the tablet Uniphyllin (U). Daily doses of 800 mg were administered at 7 p.m., half an hour after a standardized evening meal. The relative bioavailability of E with respect to U under steady-state conditions is 93 (83-105)%. In contrast to U, E markedly truncates the high peak concentrations and leads to a sustained, plateau-like concentration throughout the night. Therefore prediction of individual maximum serum levels becomes possible for E on the basis of one blood sample taken in the morning. The significantly improved in vivo performance of E in comparison with U is reflected in a 50% reduction of the swing, a 60% increase in the plateau time, and a substantial reduction of theophylline-specific side effects such as nausea, palpitations and increased diuresis.