The d-enantiomer form of indobufen totally accounts for the anti-cyclooxygenase and antiplatelet activity ex vivo and for the increase in bleeding time by indobufen in man.
Indobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean +/- S.D., 58.7 +/- 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 +/- 3% for both treatments). At 12 h inhibition was 87 +/- 6% for d-indobufen and 88 +/- 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
De Caterina
R
R
Laboratory for Thrombosis and Vascular Research, CNR Institute of Clinical Physiology, Pisa, Italy.
Sicari
R
R
Yan
A
A
Bernini
W
W
Giannessi
D
D
Lazzerini
G
G
Efthymiopoulos
C
C
Strolin-Benedetti
M
M
D000368:Aged; D001760:Bleeding Time; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054833:Isoindoles; D008297:Male; D008875:Middle Aged; D010654:Phenylbutyrates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011446:Prospective Studies; D013237:Stereoisomerism
D016861:Cyclooxygenase Inhibitors; D054833:Isoindoles; D010654:Phenylbutyrates; D010975:Platelet Aggregation Inhibitors; C020371:indobufen