COMPARATIVE EFFECTS OF NABUMETONE, SULINDAC, AND INDOMETHACIN ON URINARY PROSTAGLANDIN EXCRETION AND PLATELET-FUNCTION IN VOLUNTEERS

Nonsteroidal antiinflammatory drugs differ with respect to their effec ts on prostaglandin metabolism in various tissues, a property that may be partly responsible for some of the differences in the pharmacologi c activities and side-effect profiles that are associated with their u se. The effects of nabumetone on urinary prostaglandin excretion have not been reported. Fourteen healthy females, age 21-43 years, were tre ated 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 treatm ent on urinary prostaglandin excretion (PGE(2), 6-keto-PGF1(alpha), PG F(2 alpha), thromboxane [TX] B-2) and platelet function (collagen-indu ced 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 prostan oid, but the pattern of excretion differed in response to each drug. T reatment with NAB significantly increased the urinary excretion rates of PGE(2) and PGF(2 alpha), but 6-keto-PGF(1 alpha) and TXB(2) excreti on were unchanged. IND treatment did not result in a significant chang e in PGE(2) excretion but did significantly reduce urinary 6-keto-PGF( 1 alpha) and TXB(2) excretion rates. Reduced excretion of PGF(2 alpha) was observed on both study days during treatment with IND and SUL. SU L treatment also resulted in increased urinary PGE(2) excretion while significantly reducing 6-keto-PGF(1 alpha) excretion on day 7. Signifi cant differences were observed between the NAB and SUL regimens with r espect to PGF(2 alpha) excretion and between the NAB and SUL regimens for PGE(2), PGF(2 alpha), 6-keto-PGF(alpha 1) (on day 1 only) and TXB( 2) (on day 1 only). Neither NAB nor SUL caused inhibition of CIPA or b leeding time although platelet aggregation was inhibited during IND tr eatment. That NAB treatment was neither associated with alterations in platelet function nor decreases in the urinary excretion of the vasod ilatory prostaglandins, PGE(2) and 6-keto-PGF(1 alpha), suggests that NAB possesses renal sparing properties.