Phospholipid association reduces the gastric mucosal toxicity of aspirin in human subjects

OBJECTIVE: In previous studies on rats, we have shown that aspirin (ASA)-in duced injury to the gastric mucosa is markedly reduced or completely abolis hed if ASA is chemically associated with the phospholipid, phosphatidylchol ine (PC). We have also shown that the protective effect of PC does not infl uence the ability of ASA to inhibit mucosal cyclooxygenase (COX) activity i n the stomach and other tissues. We therefore sought to assess the effect o f PC-associated ASA (ASA/PC) on the gastric mucosa of normal volunteers and to compare the results with the use of ASA alone. METHODS: Sixteen normal healthy subjects were administered ASA or ASA/PC in a randomized, double-blind, crossover study. The subjects received ASA in a dose of 650 mg three times a day for 3 days or an equivalent dose of ASA chemically associated with PC. Endoscopy was performed at baseline and agai n on the morning of day 4, after the subjects had taken the final dose of t he test drug. On both occasions, antral biopsy specimens were obtained for the assessment of mucosal COX activity and prostaglandin concentration, RESULTS: The number (mean rt SD) of gastric erosions seen with the ASA/PC f ormulation was significantly less than when ASA was used alone (8.7 +/- 10. 7 vs 2.9 +/- 4.3; p < 0.025). A similar trend was seen in the duodenum but the difference was statistically not significant. The antral mucosal COX ac tivity, as well as the level of prostaglandin 6-keto PGF(1 alpha), were red uced significantly (80-88%) and to a similar extent by both ASA and ASA/PC. CONCLUSIONS: The present study shows that acute aspirin-induced damage to t he gastric mucosa can be reduced by chemically associating ASA with PC. The mechanism of mucosal protection provided by this compound is not related t o any alteration in the ability of ASA to inhibit mucosal COX activity. We believe this protection is attributable to the maintenance of the defensive hydrophobic barrier of the gastric mucosa. (Am J Gastroenterol 1999;94:181 8-1822. (C) 1999 by Am. Coll. of Gastroenterology).