Effects of nabumetone on prostanoid biosynthesis in humans.

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Cipollone F, Ganci A, Panara MR, Greco A, Cuccurullo F, Patrono C, Patrignani P

Effects of nabumetone on prostanoid biosynthesis in humans.

Clin Pharmacol Ther. 1995 Sep;58(3):335-41.

PubMed ID

7554708 [ View in PubMed

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Abstract

BACKGROUND: The active metabolite of the anti-inflammatory drug nabumetone has been characterized as a selective inhibitor of the inducible prostaglandin H synthase (PGHS). The aim of this study was to investigate the rate of eicosanoid biosynthesis after oral dosing with nabumetone in nine healthy subjects. METHODS: We measured the urinary excretion of products of platelet (11-dehydro-thromboxane B2 [TXB2]) and renal (prostaglandin IF2 alpha [PGF2 alpha]) arachidonate metabolism as in vivo indexes of the constitutive PGHS-1 pathway. Moreover, the production of TXB2 during whole blood clotting was assessed as an index of the cyclooxygenase activity of platelet PGHS-1 ex vivo. RESULTS: At steady state, nabumetone (500 and 1000 mg daily for 7 days) was associated with statistically significant dose-dependent reduction in the urinary excretion of 11-dehydro-TXB2 and serum TXB2 levels by approximately 50% to 70%. However, the drug did not significantly affect the urinary excretion of PGF2 alpha. After discontinuation of nabumetone, urinary 11-dehydro-TXB2 excretion and whole blood TXB2 production returned to predrug levels with a similar timecourse that was consistent with the elimination half-life of its active metabolite. The daily administration of low-dose aspirin (40 mg), a selective inhibitor of platelet PGHS-1, caused a cumulative inhibition of urinary 11-dehydro-TXB2 and whole blood TXB2 production that recovered with a timecourse consistent with platelet turnover. CONCLUSIONS: Nabumetone does dose-dependently inhibit the cyclooxygenase activity of platelet PGHS-1 of healthy subjects both in vivo and ex vivo. Thus it is unlikely that its safety profile in patients may be related to selective inhibition of the inducible PGHS-2.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Nabumetone	Prostaglandin G/H synthase 1	Protein	Humans	Unknown	Inhibitor	Details

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Nabumetone	Approved	Thromboxane B2	decreased	Nabumetone decreases the level of Thromboxane B2 in the blood