Comparative effects of nabumetone, sulindac, and indomethacin on urinary prostaglandin excretion and platelet function in volunteers.
Nonsteroidal antiinflammatory drugs differ with respect to their effects on prostaglandin metabolism in various tissues, a property that may be partly responsible for some of the differences in the pharmacologic activities and side-effect profiles that are associated with their use. The effects of nabumetone on urinary prostaglandin excretion have not been reported. Fourteen healthy females, age 21-43 years, were treated with nabumetone (NAB) 1000 mg daily, sulindac (SUL) 200 mg every 12 hours, and indomethacin (IND) 50 mg every 12 hours for 7 days in a randomized period-balanced crossover study. The effects of drug treatment on urinary prostaglandin excretion (PGE2, 6-keto-PGF1 alpha, PGF2 alpha, thromboxane [TX] B2) and platelet function (collagen-induced whole blood platelet aggregation [CIPA] and template bleeding time) were determined on day 1 and day 7. For each treatment regimen, mean baseline urinary PG excretion values were comparable for each prostanoid, but the pattern of excretion differed in response to each drug. Treatment with NAB significantly increased the urinary excretion rates of PGE2 and PGF2 alpha, but 6-keto-PGF1 alpha and TXB2 excretion were unchanged. IND treatment did not result in a significant change in PGE2 excretion but did significantly reduce urinary 6-keto-PGF1 alpha and TXB2 excretion rates. Reduced excretion of PGF2 alpha was observed on both study days during treatment with IND and SUL. SUL treatment also resulted in increased urinary PGE2 excretion while significantly reducing 6-keto-PGF1 alpha excretion on day 7. Significant differences were observed between the NAB and SUL regimens with respect to PGF2 alpha excretion and between the NAB and SUL regimens for PGE2, PGF2 alpha, 6-keto-PGF alpha 1 (on day 1 only) and TXB2 (on day 1 only). Neither NAB nor SUL caused inhibition of CIPA or bleeding time although platelet aggregation was inhibited during IND treatment. That NAB treatment was neither associated with alterations in platelet function nor decreases in the urinary excretion of the vasodilatory prostaglandins, PGE2 and 6-keto-PGF1 alpha, suggests that NAB possesses renal sparing properties.
Freed
M I
MI
Clinical Research Unit, SmithKline Beecham, Presbyterian Medical Center of Philadelphia, PA 19104.
Audet
P R
PR
Zariffa
N
N
Krishna
G G
GG
Ilson
B E
BE
Everitt
D E
DE
Brown
L E
LE
Rizzo
S M
SM
Nichols
A I
AI
Jorkasky
D K
DK
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects*; D002074:Butanones / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D000077430:Nabumetone; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000652:urine*; D013467:Sulindac / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D011453:Prostaglandins; D013467:Sulindac; D000077430:Nabumetone; D007213:Indomethacin