Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury.
OBJECTIVE
To determine if a dose of aspirin exists that might inhibit thromboxane-dependent platelet function without causing gastric mucosal injury, we studied the effects of a wide range of doses of aspirin (3 mg/d to 2600 mg/d) on gastric juice prostaglandins (PGE2 and PGF2 alpha), on serum thromboxane B2, and on stomach mucosal injury as reflected by gastric juice hemoglobin and DNA concentrations.


METHODS
A randomized, placebo-controlled study.


METHODS
Research laboratory at a Veterans Affairs medical center.


METHODS
16 healthy volunteers (5 men and 11 women).


METHODS
In the first part of the study, volunteers received placebo; aspirin, 324 mg/d; 1300 mg/d; or 2600 mg/d for 2 days. In the second part, volunteers received placebo; aspirin, 3 mg/d; 10 mg/d; 30 mg/d; or 81 mg/d for 8 days.


METHODS
Gastric juice PGE2 and PGF2 alpha, hemoglobin and DNA concentrations; gastric juice volume and acidity; and serum salicylate and thromboxane B2 concentrations.


RESULTS
In the first part, significant and similar (approximately 50%) inhibition of gastric juice prostaglandin output was observed with daily aspirin doses of 324 to 2600 mg. However, a significant increase in gastric juice hemoglobin output occurred only with 2600 mg/d. In the second part, significant inhibition (approximately 50%) of gastric PGE2 output was noted at a daily aspirin dose of 30 mg. Lower aspirin doses did not reduce PGE2 output significantly, although these doses did significantly reduce serum thromboxane B2 in a dose-related manner.


CONCLUSIONS
Aspirin can significantly reduce serum thromboxane B2 at doses of 3 mg/d or 10 mg/d, which are significantly below the threshold dose for significant gastric prostaglandin inhibition and acute stomach mucosal injury.
Lee
M
M
University of Texas Southwestern Medical Center, Dallas.
Cryer
B
B
Feldman
M
M
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects* / Q000097:blood; D004247:DNA / Q000187:drug effects; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005745:Gastric Acidity Determination; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006454:Hemoglobins / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000378:metabolism*; D012016:Reference Values; D013929:Thromboxane B2 / Q000097:blood
D006454:Hemoglobins; D011453:Prostaglandins; D013929:Thromboxane B2; D004247:DNA; D015237:Dinoprost; D015232:Dinoprostone; D001241:Aspirin