Activated aluminum complex derived from solubilized antacids exhibits enhanced cytoprotective activity in the rat.
Removing the buffering capacity of aluminum-containing antacids by acidification greatly increased their cytoprotective activity over the parent antacid. Commercially available antacids were acidified with 6 N HCl. Peak mucosal protective activity occurred at pH 2.5, and declined at lower pH. At pH 2.5, the antacid suspensions became solubilized and no acid-neutralizing capacity remained. This solution was named activated aluminum complex. Based on aluminum ion content, each aluminum-containing antacid suspension tested demonstrated a comparable increase in potency on acidification against ethanol-induced lesions. HCl (pH 2.5) was inactive against ethanol-induced lesions. At cytoprotective doses, activated aluminum complex did not cause gastric lesions when orally administered by itself, demonstrating that it is not acting as a local mucosal irritant. The data suggest that solubilization of aluminum-containing antacids in acidic medium enhances their mucosal protective activity, probably by releasing an activated species of aluminum ion reported to be a hexaaquoaluminum cation.
DiJoseph
J F
JF
Department of Immunopharmacology, Wyeth-Ayerst Research Inc., Princeton, New Jersey.
Borella
L E
LE
Mir
G N
GN
D000535:Aluminum / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000818:Animals; D000863:Antacids / Q000494:pharmacology*; D002021:Buffers; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology*; D008276:Magnesium Hydroxide / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
D000863:Antacids; D002021:Buffers; D000431:Ethanol; D000536:Aluminum Hydroxide; C016545:magaldrate; D000535:Aluminum; D008274:Magnesium; D008276:Magnesium Hydroxide