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

Abstract：

: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 pKa 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 pKa<7 (dapsone, metronidazole, cimetidine) were strongly fixed in acid medium (?62%), and fully released under neutral conditions. Amphoteric (fluoroquinolones) and basic compounds with a pKa>/=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 (>/=80%) in their available free fraction. Ionisation of drug substances administered per os concomitantly with diosmectite plays a crucial role in these interactions.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Castela-Papin N,Cai S,Vatier J,Keller F,Souleau CH,Farinotti R

doi

10.1016/s0378-5173(99)00073-3

keywords:

subject

Has Abstract

pub_date

1999-05-10 00:00:00

pages

111-9

issue

1

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(99)00073-3

journal_volume

182

pub_type

杂志文章

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