Time course and pattern of blood loss with ibuprofen treatment in healthy subjects.
OBJECTIVE
Nonselective nonsteroidal anti-inflammatory drug (NSAID) users are at increased risk of gastrointestinal bleeding. We aimed to assess the pattern and extent of fecal blood loss (FBL) with ibuprofen, which is considered to have a favorable gastrointestinal safety profile.


METHODS
We conducted a post hoc analysis of 2 separate randomized, parallel-group, double-blind studies, in which ibuprofen was used as a positive control. FBL was measured by radioactive analysis of chromium-51 labeled red cells in stools during baseline and then followed by 4 weeks of treatment with ibuprofen (800 mg 3 times daily) or placebo in 68 healthy volunteers. FBL was considered significant when blood loss was >2 mL daily.


RESULTS
The baseline period was identical for all subjects, with an average FBL of 0.36 mL (standard deviation, +/-0.075) per day. During the study period, all subjects receiving ibuprofen had a daily mean FBL >2 mL, with a group daily mean loss 3.64-fold greater than in the placebo group (2.55 mL [+/-3.2] vs 0.7 mL [+/-0.37], P < .001). In the ibuprofen group (n = 31), 26 subjects had between 1 and 7 random episodes of microbleeding with FBL >3 mL. Nine had a maximum FBL >10 mL (29.35 +/- 23.32 mL), and in 2 subjects blood loss reached 73 mL and 66 mL, respectively.


CONCLUSIONS
Treatment with a therapeutic dose of ibuprofen, a commonly used nonselective NSAID, in healthy subjects is associated with significant FBL, which occurs randomly with spikes of bleeding, sometimes exceeding 66 mL in a single day. Chronic anemia or gastrointestinal bleeding in patients taking nonselective NSAIDs should be thoroughly investigated.
Bowen
Barry
B
McMaster University Health Sciences Centre, Hamilton, Ontario, Canada L8N 3Z5.
Yuan
Yuhong
Y
James
Cindy
C
Rashid
Ferid
F
Hunt
Richard H
RH
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002857:Chromium; D002860:Chromium Radioisotopes; D004311:Double-Blind Method; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009780:Occult Blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002860:Chromium Radioisotopes; D002857:Chromium; D007052:Ibuprofen