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Comparative Effects of Nabumetone, Sulindac, and Indomethacin on Urinary Prostaglandin Excretion and Platelet Function in Volunteers
Author(s) -
Freed Martin I.,
Audet Patricia R.,
Zariffa Nevine,
Krishna G. Gopal,
Ilson Bernard E.,
Everitt Daniel E.,
Brown Linda E.,
Rizzo Susan M.,
Nichols Alice I.,
Jorkasky Diane K.
Publication year - 1994
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1994.tb01987.x
Subject(s) - excretion , nabumetone , medicine , endocrinology , urinary system , chemistry , prostaglandin , platelet , nonsteroidal
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 (PGE 2 , 6‐keto‐PGF 1α , PGF 2α , thromboxane [TX] B 2 ) 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 PGE 2 and PGF 2α , but 6‐keto‐PGF1 α and TXB 2 excretion were unchanged. IND treatment did not result in a significant change in PGE 2 excretion but did significantly reduce urinary 6‐keto‐PGF 1α and TXB 2 excretion rates. Reduced excretion of PGF 2α was observed on both study days during treatment with IND and SUL. SUL treatment also resulted in increased urinary PGE 2 excretion while significantly reducing 6‐keto‐PGF 1α excretion on day 7. Significant differences were observed between the NAB and SUL regimens with respect to PGF 2α excretion and between the NAB and SUL regimens for PGE 2 , PGF 2α , 6‐keto‐PGF α1 (on day 1 only) and TXB 2 (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, PGE 2 and 6‐keto‐PGF 1α , suggests that NAB possesses renal sparing properties.