Aspirin dosage and thromboxane synthesis in patients with vascular disease.
OBJECTIVE
To determine whether urinary 11-dehydrothromboxane B2 (d-TXB2) is a marker of aspirin resistance and define the relationship between aspirin dosage and concentrations of this thromboxane metabolite.


METHODS
Randomized, crossover study.


METHODS
Two outpatient clinical centers.


METHODS
Forty-eight patients (mean age 70 yrs) with vascular disease (52% clinical coronary artery disease, 29% cerebrovascular disease, 46% atrial fibrillation).


METHODS
Levels of serum thromboxane B2 and d-TXB2 were measured after patients were treated initially with aspirin 325 mg/day for 4 weeks, then again after random assignment to receive aspirin 81, 325, or 1300 mg/day for 4 weeks, and then again after resumption of 325 mg/day for 4 weeks.


RESULTS
During treatment with aspirin 325 mg/day, the mean +/- SD serum thromboxane B2 level was 0.9 +/- 1.2 ng/ml and median (interquartile range) was 0.4 (0.2-0.9) ng/ml. Mean urinary d-TXB2 was 16 +/- 7.9 ng/mmol creatinine, with a median of 15 (9.9-23) ng/mmol creatinine with aspirin 325 mg/day. After 4 weeks of aspirin 81 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p=0.04) were both significantly higher compared with aspirin 325 mg/day; for urinary d-TXB2, the median increase was 3.0 ng/mmol creatinine. After 4 weeks of treatment with aspirin 1300 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p<0.01) were both significantly lower compared with aspirin 325 mg/day; the median decrease in urinary d-TXB2 was 4.4 ng/mmol creatinine.


CONCLUSIONS
Different aspirin dosages significantly affect serum and urinary markers of thromboxane synthesis.
Hart
Robert G
RG
University of Texas Health Science Center, San Antonio 78229-3900, USA.
Leonard
Anne D
AD
Talbert
Robert L
RL
Pearce
Lesly A
LA
Cornell
Elaine
E
Bovill
Edwin
E
Feinberg
William M
WM
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D014652:Vascular Diseases / Q000097:blood / Q000378:metabolism* / Q000652:urine
D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D001241:Aspirin