Effect of omeprazole on the bioavailability of unmodified and phospholipid‐complexed aspirin in rats

• Published in: Alimentary pharmacology & therapeutics Vol. 11; no. 5; pp. 899 - 906
• Main Authors: GIRAUD, M.‐N., SANDUJA, S. K., FELDER, T. B., ILLICH, P. A., DIAL, E. J., LICHTENBERGER, L. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.10.1997; Blackwell
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - chemistry; 6-Ketoprostaglandin F1 alpha - metabolism; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Aspirin - blood; Aspirin - chemistry; Aspirin - pharmacokinetics; Biological and medical sciences; Biological Availability; Drug Carriers; Drug toxicity and drugs side effects treatment; Enzyme Inhibitors - pharmacology; Gastric Mucosa - metabolism; Male; Medical sciences; Neutralization Tests; Omeprazole - pharmacology; Pharmacology. Drug treatments; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; Toxicity: digestive system; Rat; Toxicity; H; Phospholipid; Antiulcer agent; Acetylsalicylic acid; K; Prevention; Antisecretory agent; Secondary effect; Drug interaction; Salicylates; Gastric disease; Complexation; Drug combination; Enzyme; Controlled release form; Rodentia; Enzyme inhibitor; Bioavailability; Non steroidal antiinflammatory agent; Omeprazole; Intragastric administration; Vertebrata; Chemotherapy; Mammalia; Analgesic; Treatment; Animal; Distribution; Digestive diseases; Hydrolases; exchanging ATPase; Pharmacokinetics
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1046/j.1365-2036.1997.00216.x

Background: Treatment and prevention of non‐steroidal anti‐inflammatory drug‐induced gastropathy involve the concurrent use of antisecretory drugs. Recently, we have shown that the ability of these drugs to increase the intragastric pH to values pKa of NSAIDs compromises their therapeutic activity. In the present study, we evaluated the potential of omeprazole to interfere with the bioavailability of aspirin administered to rats either alone or complexed with the zwitterionic phospholipid, dipalmitoylphosphatidylcholine (DPPC). Methods: Aspirin or aspirin/DPPC was administered intragastrically to rats pre‐dosed with either saline or omeprazole. Concentrations of aspirin and salicylic acid in the blood and the gastric mucosa were assessed by HPLC and the 6‐keto‐PGF1α gastric mucosal concentration by radioimmunoassay. Results: Gastric absorption of aspirin and its relative bioavailability were reduced by an antisecretory dose of omeprazole; its inhibitory effect on gastric prostaglandin synthesis was consequently attenuated. However, these effects could be partly overcome if aspirin was administered as a complex with DPPC. Conclusions: These observations suggest that: (i) DPPC increases the lipid solubility and gastric permeability of NSAIDs; and (ii) neutralization of the gastric pH results in a shift of aspirin absorption toward the intestine where it could be degraded to salicylic acid.