Nabumetone - How It Works
Clinical pharmacology details from the US FDA-approved label: how Nabumetone works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
CLINICAL PHARMACOLOGY Nabumetone is a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic properties in pharmacologic studies.
As with other non-steroidal anti-inflammatory agents, its mode of action is not known; however, the ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.
The parent compound is a prodrug, which undergoes hepatic biotransformation to the active component, 6-methoxy-2-naphthylacetic acid (6MNA) that is a potent inhibitor of prostaglandin synthesis.
6-methoxy-2-naphthylacetic acid (6MNA) It is acidic and has an n-octanol: phosphate buffer partition coefficient of 0.5 at pH 7.4.
6MNA Pharmacokinetics: After oral administration, approximately 80% of a radiolabeled dose of nabumetone is found in the urine, indicating that nabumetone is well absorbed from the gastrointestinal tract.
Nabumetone itself is not detected in the plasma because, after absorption, it undergoes rapid biotransformation to the principal active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA).
Approximately 35% of a 1,000-mg oral dose of nabumetone is converted to 6MNA and 50% is converted into unidentified metabolites which are subsequently excreted in the urine.
Following oral administration of nabumetone, 6MNA exhibits pharmacokinetic characteristics that generally follow a one-compartment model with first order input and first order elimination.
6MNA is more than 99% bound to plasma proteins.
The free fraction is dependent on total concentration of 6MNA and is proportional to dose over the range of 1,000 mg to 2,000 mg.
It is 0.2% to 0.3% at concentrations typically achieved following administration of 1,000 mg of nabumetone and is approximately 0.6% to 0.8% of the total concentrations at steady state following daily administration of 2,000 mg.
Steady-state plasma concentrations of 6MNA are slightly lower than predicted from single-dose data.
This may result from higher fraction of unbound 6MNA which undergoes greater hepatic clearance.
Coadministration of food increases the rate of absorption and subsequent appearance of 6MNA in the plasma but does not affect the extent of conversion of nabumetone into 6MNA.
Peak plasma concentrations of 6MNA are increased by approximately one third.
Coadministration with an aluminum-containing antacid had no significant effect on the bioavailability of 6MNA.
Mean Pharmacokinetic Parameters of Nabumetone Active Metabolite (6MNA) at Steady State Following Oral Administration of 1,000-mg or 2,000-mg Doses of nabumetone Abbreviation (units) Young Adults Mean ± SD 1,000 mg n = 31 Young Adults Mean ± SD 2,000 mg n = 12 Elderly Mean ± SD 1,000 mg n = 27 T max (hr) 3.0 (1.0 to 12.0) 2.5 (1.0 to 8.0) 4.0 (1.0 to 10.0) t ½ (hr) 22.5 ± 3.7 26.2 ± 3.7 29.8 ± 8.1 CL ss /F (ml/min) 26.1 ± 17.3 21.0 ± 4.0 18.6 ± 13.4 Vd ss /F (L) 55.4 ± 26.4 53.4 ± 11.3 50.2 ± 25.3 The simulated curves in the graph below illustrate the range of active metabolite plasma concentrations that would be expected from 95% of patients following 1,000-mg to 2,000-mg doses to steady state.
The cross-hatched area represents the expected overlap in plasma concentrations due to intersubject variation following oral administration of 1,000 mg to 2,000 mg of nabumetone.
6MNA undergoes biotransformation in the liver, producing inactive metabolites that are eliminated as both free metabolites and conjugates.
None of the known metabolites of 6MNA has been detected in plasma.
Pharmacokinetics
Pharmacokinetics: After oral administration, approximately 80% of a radiolabeled dose of nabumetone is found in the urine, indicating that nabumetone is well absorbed from the gastrointestinal tract. Nabumetone itself is not detected in the plasma because, after absorption, it undergoes rapid biotransformation to the principal active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). Approximately 35% of a 1,000-mg oral dose of nabumetone is converted to 6MNA and 50% is converted into unidentified metabolites which are subsequently excreted in the urine. Following oral administration of nabumetone, 6MNA exhibits pharmacokinetic characteristics that generally follow a one-compartment model with first order input and first order elimination. 6MNA is more than 99% bound to plasma proteins. The free fraction is dependent on total concentration of 6MNA and is proportional to dose over the range of 1,000 mg to 2,000 mg. It is 0.2% to 0.3% at concentrations typically achieved following administration of 1,000 mg of nabumetone and is approximately 0.6% to 0.8% of the total concentrations at steady state following daily administration of 2,000 mg. Steady-state plasma concentrations of 6MNA are slightly lower than predicted from single-dose data. This may result from higher fraction of unbound 6MNA which undergoes greater hepatic clearance. Coadministration of food increases the rate of absorption and subsequent appearance of 6MNA in the plasma but does not affect the extent of conver