Effects of acetylsalicylic acid on ascorbic acid concentrations in plasma, gastric mucosa, gastric juice and urine--a double-blind study in healthy subjects.
OBJECTIVE
This study investigated concentrations of ascorbic acid (ASC) in gastric mucosa, gastric juice, urine and plasma in healthy subjects under steady state and fasted conditions with and without concomitant administration of acetylsalicylic acid (ASA).


METHODS
This was a prospective, randomized, double-blind, parallel-group study in healthy subjects. It has assessed the effects of a 6-day administration of 0.8 g ASA or 0.48 g ASC, 3 times daily and the combination of both on concentrations of ASC in gastric mucosa, gastric juice, urine and plasma. Treatments were switched after 6 days without any washout for assessment of compartment sensitivity to changes in study medication resulting in an overall 14-day study period. Each of the 3 treatment groups consisted of 15 subjects.


RESULTS
ASC concentrations were highest in the gastric mucosa (251+/-11 microg/g), followed by gastric juice (29+/-6 microg/ml), plasma (10+/-0.2 microg/ml), and urine (5+/-1 microg/ml). On day 7, ASC concentrations in gastric mucosa, plasma and urine had increased in those groups receiving ASC and decreased in the group receiving ASA only. All differences were statistically significant and indicate an interaction with ASA. In gastric juice, differences in ASC concentrations between the treatment groups were not statistically significant between baseline and day 7. ASC concentrations in plasma were strongly correlated with corresponding ASC concentrations in gastric mucosa (r = 0.34) and urine (r = 0.83), as were ASC concentrations in gastric mucosa with ASC in urine (r = 0.28).


CONCLUSIONS
The gastric mucosa is the largest depot of ASC in the human body with ASC concentrations 25 times higher than in plasma. In healthy subjects, clinically relevant doses of ASA reduced ASC concentrations in gastric mucosa by about 10% within 6 days resulting from antioxidative defense mechanisms. In patients with long-term ASA treatment or conditions with additional risks such as elderly subjects with unfavorable dietary conditions and impaired antioxidative protection, a protective adjunct administration of ASC appears to be beneficial.
Schulz
H U
HU
LAFAA Laboratory for Contract Research in Clinical Pharmacology and Biopharmaceutical Analytics GmbH, Bad Schwartau, Germany. lafaa_gmbh@t-online.de
Schürer
M
M
Krupp
S
S
Dammann
H G
HG
Timm
J
J
Gessner
U
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001205:Ascorbic Acid; D001241:Aspirin