Influence of food on the absorption of theophylline administered in the form of sustained release tablet and microgranules.
Two sustained-release formulations of theophylline, tablets (T) and microgranules (MG) forms, were administered in a randomized order to 8 healthy subjects in fasting or with a high-protein test meal (50 per cent). Blood was collected for 32h post-dose. In fasting subjects, absorption of theophylline was significantly faster for T (tmax 5 h) as compared with MG (tmax 8 h, p less than 0.05), but Cmax and AUC were comparable; intersubject variability was higher with T. Administration of a high-protein test meal with T produced a significant decrease of the zero-order absorption rate constant of theophylline (K omicron 37.8 +/- 9.1 mgh-1 after meal versus 58.8 +/- 13 mgh-1 in fasting, p = 0.01), tmax was doubled to 10 h, and Cmax increased by 25 per cent (6.33 +/- 2.16 mgl-1 versus 5.04 +/- 1.28 mgl-1, p less than 0.02); with MG, tmax were the same (8 h), Cmax were not significantly increased (4.79 +/- 0.84 mgl-1 versus 4.55 +/- 0.67 mgl-1), absorption was delayed (lag-time 1.28 +/- 0.58 h) and the absorption was slightly accelerated (K omicron 50.4 +/- 10.4 mgh-1 versus 42.3 +/- 11.9 mgh-1, NS). For each form bioavailability was not significantly modified by food. This study demonstrated that food rich in protein modifies the absorption rate of theophylline in a sustained-release tablet formulation but is without influence in a pH-independent, sustained-release microgranule formulation.
Delhotal-Landes
B
B
Department of Clinical Pharmacology, Ambroise Paré Hospital, Boulogne-Billancourt, France.
Flouvat
B
B
Boutin
M S
MS
Karpouzas
I
I
Prinseau
J
J
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004044:Dietary Proteins / Q000008:administration & dosage; D005502:Food; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D004044:Dietary Proteins; D013806:Theophylline