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- W2315204401 abstract "Nabumetone, a new anti-inflammatory drug, was studied in six healthy male volunteers to evaluate its steady-state pharmacokinetics after oral dosing. The subjects were given a single dose of 800 mg, followed by 800 mg once a day for seven days after a washout period of two weeks. The plasma (or serum) and urinary concentrations of nabumetone, and its metabolites BRL 10720 or BRL 18725 were determined by high performance liquid chromatography. Nabumetone was extensively metabolized mainly to its active form BRL 10720 after oral dosing. The pharmacokinetics of BRL 10720 were well described by one-compartment model with first-order input. The plasma concentrations of BRL 10720 reached steady state by the fourth day of multiple dosing with 1.52 times accumulation of trough concentration and declined with a half-life of 19.2 hours after the last dose. The mean plasma concentration at steady state was 34.9 μg/ml. The AUC from time zero to 24 hours at the steady state was 26.6 % lower than the AUC from time zero to infinity after single dosing. BRL 10720 was extensively bound to serum proteins with range from 99.75 to 99.91 % in a concentration-dependent manner. The plasma concentrations of nabumetone and BRL 18725 were very low and were about 1/1500 times or less than that of BRL 10720. Urinary excretion of BRL 10720 was very small and 2.32 % of the dose was recovered in 72 hours after single dosing, while 25.6 % of the dose as the total amount of BRL 10720 and its conjugated form. Only negligible amounts of nabumetone were excreted in the urine. Nabumetone was well tolerated by all subjects. Clinically significant adverse effects were not observed." @default.
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- W2315204401 date "1988-01-01" @default.
- W2315204401 modified "2023-09-24" @default.
- W2315204401 title "Steady-state Pharmacokinetics of Oral Nabumetone in Man" @default.
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- W2315204401 doi "https://doi.org/10.2133/dmpk.3.407" @default.
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