Influence of hyperlipidic food on the kinetics of slow-release formulations of theophylline

A cross-over study of kinetics has been undertaken in 12 healthy adults volunteers using two sustained-release theophylline products that allow once a day dosing (Theo-Dur tablets and Dilatrane A.P. bead filled capsules) to compare the i.v. pharmacokinetic profiles when taken with an hyperlipidic meal and a balanced standard meal. Each subject took part in four phases in randomised order, corresponding to all possible combinations of the products and the types of meal. Each phase involved a single dose of 9 to 11 mg.kg-1 theophylline administered at 20.00 h, at the beginning of the meal, with 100 ml water. The two formulations were found to be bioequivalent with both types of meal. Taken with a balanced meal, the mean parameters were similar; for Theo-Dur and Dilatrane A.P. they were respectively: Cmax: 11.32 mg.l-1 which plateaued from 8 to 10 h after dosing and 10.9 mg.l-1, which plateaued after 6 to 10 h; AUC 230 mg.h.l-1 and 220 mg.h.l-1; and MRT 18.2 h and 17.7 h. After the hyperlipidic meal the values for Theo-Dur and Dilatrane A.P. respectively, were: Cmax 10.9 mg.l-1 at 12 h and 11.3 mg.l-1 at 10 h; AUC 237 mg.h.l-1 and 227 mg.h.l-1; and MRT 19.2 h and 18.9 h. In spite of a decrease in the absorption rate, which led to a shift to the right of about 2 h of the plasma concentration-time curve, the bioavailability of both formulations were not significantly modified by a hyperlipidic meal as compared to a balanced meal.