Drug interactions with diosmectite: a study using the artificial stomach-duodenum model

Drug interactions with diosmectite, a gastric-protective drug, were studied in vitro using an artificial stomach-duodenum model. The behavior of neutral and ionisable drugs with pK(a) values ranging between 2 and 8 was monitored to determine the physicochemical characteristics of the interactions. The main neutral (digoxin) and acid (valproic acid) drug substances were moderately fixed by clay (<27%), in a pH-independent manner. Basic compounds with a pK(a) <7 (dapsone, metronidazole, cimetidine) were strongly fixed in acid medium (>62%), and fully released under neutral conditions. Amphoteric (fluoroquinolones) and basic compounds with a pK(a) greater than or equal to 7 (ranitidine, pyrimethamine) were adsorbed by more than 81% by diosmectite in gastric and duodenal compartments. In the part of the model representing the distal duodenum, the potential site for drug absorption, only the active substances which remained positively charged (amphoteric and basic compounds) showed a large reduction (greater than or equal to 80%) in their available free fraction. lonisation of drug substances administered per os concomitantly with diosmectite plays a crucial role in these interactions. (C) 1999 Elsevier Science B.V. All rights reserved.