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.
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000628:Aminophylline / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D001682:Biological Availability; D002110:Caffeine / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D006801:Humans; D007700:Kinetics; D008297:Male; D011897:Random Allocation; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism
D003692:Delayed-Action Preparations; D000628:Aminophylline; D002110:Caffeine; D013806:Theophylline; C021183:1,7-dimethylxanthine