Interactions of cimetidine and ranitidine with aluminum-containing antacids and a clay-containing gastric-protective drug in an "artificial stomach-duodenum" model.
Interactions of cimetidine and ranitidine with aluminum-containing antacids and clay-containing gastric-protective drugs were analyzed in vitro by using an artificial stomach-duodenum model. The model reproduced near-physiologic conditions, taking into account gastric and duodenal flux variations and interactions between gastric mucosa and drugs added to the gastric content. Clay bound cimetidine in acid medium, but the drug was released when the pH increased, resulting in cimetidine amounts in the duodenal site close to those in controls. In contrast, clay bound ranitidine in acid medium and did not release it in the duodenal site. Aluminum-containing antacids did not significantly modify the amount of cimetidine or ranitidine available for absorption. Several factors play a role in the interactions of cimetidine and ranitidine with aluminum-containing antacids and clay-containing gastric-protective drugs: the structure of the antisecretory drugs, gastroduodenal pH, interactions of the antacid and clay with the gastric mucosa, and release of aluminum that could adsorb the drugs or prevent their adsorption by the mucosa. These phenomena are intricate and difficult to analyze without using a physicochemical approach.
Vatier
J
J
INSERM U 10 Biochemistry B, Paris, France.
Harman
A
A
Castela
N
N
Droy-Lefaix
M T
MT
Farinotti
R
R
D000535:Aluminum / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D000863:Antacids / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001825:Body Fluid Compartments; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002927:Cimetidine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004347:Drug Interactions; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008954:Models, Biological; D011899:Ranitidine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D017640:Silicates; D012996:Solutions; D013270:Stomach / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D013607:Tablets
D000863:Antacids; D005765:Gastrointestinal Agents; D017640:Silicates; D012996:Solutions; D013607:Tablets; D002927:Cimetidine; D011899:Ranitidine; C033214:Smectite; D000535:Aluminum