Theophylline disposition after single-dose ingestion of a once-a-day preparation (Dilatrane A. P. 400 mg) with and without breakfast
Jonkman, J.H.; Grasmeijer, G.; Holland, A.
International Journal of Clinical Pharmacology Therapy and Toxicology 25(11): 633-637
1987
ISSN/ISBN: 0174-4879 PMID: 3429067 Document Number: 298898
In a two-way single dose crossover experiment in 12 healthy young adults the influence of food (breakfast) on the absorption profiles and bioavailability of theophylline was investigated when the drug was given as Dilatrane A. P. 400 mg capsules (Fisons), a once-a-day sustained-release preparation. The capsule was taken at 8:00 a. m. either after a 10-h fast or immediately after a standard breakfast, yielding 1990 kJ. Theophylline in plasma was measured by high pressure liquid chromatography over a period of 48 h. The food caused a slight but not significant (p greater than 0.05, Student's paired t-test) increase in the time to peak (tmax, 9.4 +/- 1.3 h vs. 8.4 +/- 1.7 h, mean +/- SD) and in the area under the curve (AUC0-48, 114.3 +/- 41.7 mg.l-1.h vs. 105.3 +/- 36.5 mg.l-1.h), the relative bioavailability being 108.9 +/- 12.4%, as compared with ingestion of the capsule in fasted state. Maximum theophylline concentrations in plasma were slightly but significantly higher (cmax, 6.50 +/- 1.82 mg.l-1 vs. 5.26 +/- 1.36 mg.l-1, p less than 0.001) after intake with food but this will probably not be of any clinical relevance. The product is considered to be of good sustained-release quality which in practice may well be taken with food in order to reduce the incidence of locally mediated theophylline-induced gastrointestinal disturbances.