Urinary prostanoid metabolites and serum thromboxane following recovery from cyclooxygenase inhibition with aspirin

A previous study that measured urinary thromboxane B2 (TXB2) and 6-keto-PGF1ɑ after with-drawal of aspirin found evidence of a rebound in urinary prostanoid excretion above control levels 14 days after aspirin administration ceased. This study aimed to confirm these findings using a wider range of prostanoid metabolites. The subjects were 17 young, healthy volunteers who had taken 100 mg of enteric-coated aspirin daily for 7 days followed by 650 mg of enteric-coated aspirin for a further 7 days as part of another study. They showed signs of the expected inhibition of TXB2 metabolites at the end of aspirin treatment. After 650 mg aspirin, serum generation of TXB2 by clotting blood was 0.77 ± 0.2% of control (p < 0.0001), urinary 1 21-dehydro-TXB2 was 21.8 ± 2.8% of control (p < 0.0001), and urinary TXB2 was 33.7 ± 4.2% of control (p < 0.0001). Fourteen days after aspirin withdrawal, TXB2 metabolites as a percentage of control were, respectively, serum TXB2 163 ± 45%; urinary 1,21-dehydro-TXB 114.4 ± 13.8%, and urinary TXB2 106.0 ± 12% (all not significant compared with control). The urinary 6-keto-PGF1ɑ level 14 days after aspirin withdrawal was 96.9 ± 17.8% of control (NS). Twenty-one days after aspirin withdrawal, TXB2 metabolites as a percentage of control were, respectively, serum TXB2 154 ± 39%; urinary TXB2 114 ± 11% (both NS compared with control; and urinary 11-dehydro, TXB2, 127.2 ± 11.9% (p = 0.037 compared with control). Urinary 6-keto-PGF1ɑ 21 days after aspirin withdrawal was 159.9 ± 46.2% of control (NS). Overall there would appear to be a trend to increased production of prostanoid metabolites 14 and 21 days after aspirin withdrawal, but it reached statistical significance only for 11-dehydro-TXB2 at 21 days' withdrawal. As platelets are the major source of this metabolite, this finding would suggest that increased platelet generation of TXB2 plays a part. Key Words: Aspirin—Platelets—Thromboxane A2. © 1995, Sage Publications. All rights reserved.