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  • Title: Differences in steady-state plasma levels between aminophylline and theophylline sustained-release micropellets after repeated circadian dosing.
    Author: Schulz HU, Steinijans VW, Gabel H.
    Journal: Int J Clin Pharmacol Ther Toxicol; 1984 Nov; 22(11):621-5. PubMed ID: 6500759.
    Abstract:
    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.
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