Effect of clopidogrel on naproxen-induced gastrointestinal blood loss in healthy volunteers

Drug Metabol Drug Interact. 1998;14(3):193-205. doi: 10.1515/dmdi.1998.14.3.193.


The effect of clopidogrel, a potent inhibitor of platelet aggregation, on naproxen-induced faecal blood loss was investigated in 30 healthy volunteers in a randomized, double-blind, placebo-controlled, two parallel treatment groups study. All subjects first received naproxen 250 mg b.i.d. during 7 days, after which they were randomly allocated to additionally receive either clopidogrel 75 mg once daily (n = 15) or matching placebo (n = 15) for 11 days. Faecal blood loss was measured by the 51Cr-labelled erythrocyte method during the last four days of each of the four study periods, i.e. baseline, treatment with naproxen alone, combined treatment and wash-out. Mean daily faecal blood loss was below 0.5 ml/day during the baseline period in both treatment groups and increased during treatment with naproxen alone to (mean +/- SD) 1.14 +/- 0.58 ml/day in the naproxen + placebo group and to 1.93 +/- 1.51 ml/day in the naproxen + clopidogrel group. Addition of clopidogrel to naproxen treatment was associated with an increase of the mean daily blood loss to 6.83 +/- 9.32 ml/day, which was statistically significantly higher than 1.75 +/- 1.40 ml/day observed during treatment with naproxen + placebo. During the wash-out period, mean daily blood loss decreased to 0.98 +/- 0.51 ml/day in the naproxen + placebo group and to 1.07 +/- 0.46 ml/day in the naproxen + clopidogrel group. Based on these results, it can be concluded that clopidogrel increases naproxen-induced gastrointestinal blood loss in healthy volunteers. Caution should therefore be called for when these drugs are coadministered.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Bleeding Time
  • Clopidogrel
  • Double-Blind Method
  • Drug Interactions
  • Gastrointestinal Hemorrhage / chemically induced*
  • Humans
  • Male
  • Naproxen / adverse effects*
  • Naproxen / pharmacokinetics
  • Occult Blood
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics


  • Anti-Inflammatory Agents, Non-Steroidal
  • Platelet Aggregation Inhibitors
  • Naproxen
  • Clopidogrel
  • Ticlopidine