Differences in steady-state plasma levels between aminophylline and theophylline sustained-release micropellets after repeated circadian dosing.

In a randomized double-blind, cross-over study, theophylline plasma levels were compared over 24 hours after repeated administration of aminophylline and theophylline sustained-release formulations to 12 healthy volunteers. Although both preparations were capsules containing micropellets, and although they were administered in an identical circadian dosing scheme (1 capsule at 8:00 a.m., 2 capsules at 10:00 p.m.), marked differences in theophylline plasma levels were found. Whereas the aminophylline micropellets (Euphyllin CR 350) resulted in the clinically desired concentration/time profile with highest theophylline plasma levels between 2:00 a.m. and 6:00 a.m., theophylline micropellets failed to do so. Apart from differences in the in-vitro release at low pH-values, this may be due to differences in solubility between aminophylline and theophylline, which become clinically relevant in the supine position at night.