Effect of food on the bioavailability of adinazolam from a sustained release formulation: Effect of meal timing and lack of dose dumping

摘要

AbstractFood effects on adinazolam absorption from sustained release (SR) adinazolam mesylate tablets were assessed in 28 healthy male volunteers. Subjects received 15 mg SR tablets. 15 mg immediate release tablets, 15 mg oral solution, administered after an overnight fast, and 15 mg SR tablets after a high fat breakfast. Treatments were administered in a crossover design. Plasma adinazolam and N‐desmethyladinazolam (NDMAD) concentrations were determined by HPLC. Adinazolam and NDMAD AUC values were unaffected by food.Cmaxfor SR tablets was increased 33 per cent and 18 per cent for adinazolam and NDMAD, respectively, when administered postprandially.Tmaxoccurred later in the fed state: no dose dumping was observed. Meal timing effects on adinazolam absorption from SR tablets were assessed in 24 healthy subjects, who received 30 mg SR tablets 1 h before, 0·5 h after, 2 h after a high fat meal, and in the fasted state. Postprandial administration had no effect on AUC, but resulted later and higher adinazolam and NDMADCmax. Differences in these values were less than 11 per cent. Administration of SR tablets before meals yieldedCmaxandTmaxvalues which were similar to the fasted state. Results suggest that meal timing does not substantially affect adinazolam absorption from the SR tabl