Effect of maximum OTC doses of naproxen sodium or acetaminophen on low-dose aspirin inhibition of serum thromboxane B2.
OBJECTIVE
This study evaluated the platelet inhibitory effects of low-dose enteric-coated aspirin (EC-ASA) when used concomitantly with maximum over-the-counter (OTC) doses of naproxen sodium (NAPSO) or acetaminophen to determine whether NAPSO and acetaminophen interfere with the anti-platelet effect of aspirin.


METHODS
Phase I, randomized, open-label, multi-dose, three-period, parallel group, pharmacodynamic trial conducted in healthy male and female volunteers (n = 47 randomized subjects and n = 37 evaluable subjects), mean age 40.2 years. All subjects received 5 days of EC-ASA 81 mg once daily followed by 5 days of EC-ASA 81 mg once daily alone or co-administered with either NAPSO 220 mg three times daily or acetaminophen 1 g four times daily.


METHODS
Inhibition of serum thromboxane B(2) (TXB(2)), as a marker of platelet cyclooxygenase-1 (COX-1) inhibition, measured on Day 11.


RESULTS
Mean inhibition of TXB(2) on Day 11 was >99% for subjects taking EC-ASA alone as well as for those who received EC-ASA co-administered with NAPSO or acetaminophen. For subjects taking EC-ASA monotherapy, mean serum TXB(2) inhibition was 99.7% (range 99.0-100%), for those taking EC-ASA with acetaminophen it was 99.6% (range 98.3-99.9%), and for those taking EC-ASA with NAPSO, mean serum TXB(2) inhibition was 99.7% (range 99.2-100%).


CONCLUSIONS
Small sample size and open-label trial design.


CONCLUSIONS
The anti-platelet effect of EC-ASA 81 mg once daily was maintained following its co-administration with maximum OTC doses of NAPSO or acetaminophen.
Oldenhof
John
J
Kendle Early Stage, Toronto, Ontario, Canada. oldenhof.john@kendle.com
Hochberg
Marc
M
Schiff
Michael
M
Brune
Kay
K
D000082:Acetaminophen / Q000008:administration & dosage / Q000378:metabolism*; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage / Q000378:metabolism*; D004366:Nonprescription Drugs / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D055815:Young Adult
D018712:Analgesics, Non-Narcotic; D016861:Cyclooxygenase Inhibitors; D004366:Nonprescription Drugs; D010975:Platelet Aggregation Inhibitors; D000082:Acetaminophen; D013929:Thromboxane B2; D009288:Naproxen; D001241:Aspirin