title: Effect of clopidogrel on naproxen-induced gastrointestinal blood loss in healthy volunteers.
abstract: 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.
authors.affiliation: Centre for Clinical Pharmacology, UZ Gasthuisberg, K.U.Leuven, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: van Hecken
authors.forename: M
authors.initials: M
authors.lastname: Depré
authors.forename: K
authors.initials: K
authors.lastname: Wynants
authors.forename: H
authors.initials: H
authors.lastname: Vanbilloen
authors.forename: A
authors.initials: A
authors.lastname: Verbruggen
authors.forename: J
authors.initials: J
authors.lastname: Arnout
authors.forename: P
authors.initials: P
authors.lastname: Vanhove
authors.forename: R
authors.initials: R
authors.lastname: Cariou
authors.forename: P J
authors.initials: PJ
authors.lastname: De Schepper
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000493:pharmacokinetics; D001760:Bleeding Time; D000077144:Clopidogrel; D004311:Double-Blind Method; D004347:Drug Interactions; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D009288:Naproxen / Q000009:adverse effects* / Q000493:pharmacokinetics; D009780:Occult Blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D009288:Naproxen; D000077144:Clopidogrel; D013988:Ticlopidine