Clinical Pharmacology of Cyclooxygenase Inhibition and Pharmacodynamic Interaction with Aspirin by Floctafenine in Thai Healthy Subjects. (April 2013)

• Record Type: Journal Article
• Authors: Maenthaisong, R.; Tacconelli, S.; Sritara, P.; Del Boccio, P.; Di Francesco, L.; Sacchetta, P.; Archararit, N.; Aryurachai, K.; Patrignani, P.; Suthisisang, C.
• Is Part Of: International journal of immunopathology and pharmacology. Volume 26:Number 2(2013)
• Page Start: 403
• Page End: 417
• Publication Date: 2013-04
• Subjects: nonsteroidal anti-inflammatory drugs -- floctafenine -- COX-1 -- COX-2 -- pharmacodynamic interaction -- aspirin; Immunopathology -- Periodicals; Pharmacology -- Periodicals; Inflammation -- Periodicals; 615.1
• DOI: 10.1177/039463201302600213
• Languages: English
• ISSNs: 0394-6320

Abstract

Floctafenine, a hydroxyquinoline derivative with analgesic properties, is widely used in Thailand and many other countries. The objectives of this study were to evaluate in Thai healthy volunteers: i) the inhibition of whole blood cyclooxygenase(COX)-2 and COX-1 activity by floctafenine and its metabolite floctafenic acid in vitro and ex vivo after dosing with floctafenine; ii) the possible interference of floctafenine administration with aspirin antiplatelet effects. We performed an open-label, cross-over, 3-period study, on 11 healthy Thai volunteers, who received consecutively floctafenine(200mg/TID), low-dose aspirin(81mg/daily) or their combination for 4 days, separated by washout periods. Floctafenine and floctafenic acid resulted potent inhibitors of COX-1 and COX-2 in vitro (floctafenic acid was more potent than floctafenine) showing a slight preference for COX-1. After dosing with floctafenine alone, whole blood COX-1 and COX-2 activities were inhibited ex vivo in a time-dependent fashion which paralleled floctafenic acid plasma concentrations. Aspirin alone inhibited profoundly and persistently platelet COX-1 activity and AA-induced platelet aggregation throughout 24-h dosing interval which was affected by the co-administration of floctafenine. At 24 h after dosing with aspirin and floctafenine, the inhibition of platelet thromboxane(TX)B2 generation [73±26%(mean±SD)] and aggregation [70(2-92)%, median(range)] were significantly(P<0.05) lower than that caused by aspirin alone [97±1.9% and 87(83–89)%, respectively]. Therapeutic dosing with floctafenine profoundly inhibited prostanoid biosynthesis through the rapid conversion to floctafenic acid. Floctafenine interfered with the antiplatelet effect of aspirin. Our results suggest that floctafenine should be avoided in patients with cardiovascular disease under treatment with low-dose aspirin.