Nabumetone
Nabumetone. Prodrug NSAID — undetectable in plasma; rapidly biotransformed to the active 6-MNA (6-methoxy-2-naphthylacetic acid), a relatively… Oral half-life 27 h.
Prodrug NSAID — undetectable in plasma; rapidly biotransformed to the active 6-MNA (6-methoxy-2-naphthylacetic acid), a relatively COX-2-preferential inhibitor. Long 6-MNA t½ (~24 h) → once-daily dosing.
PK models 6-MNA, the circulating active metabolite (nabumetone is a prodrug). Daigneault 1987 (PMID:3687999), 24 healthy men, 1 g tablet: verbatim "absorption half-life = 1.04 … elimination half-life = 27.16 … hours", Tmax 4.99 h; ka = ln2/1.04 h = 0.67 /h. Steady-state t½ 22.77/22.0 h (PMID:6526543) corroborates. V and F are not stated for healthy subjects in any abstract (Brier 1995, PMID:7781261, gives an apparent V of 23–60 L across a renal-impairment population) and are left to solver defaults. PK: THE ERRORS COMPENSATED, EXACTLY AS THE ATRACURIUM CASE TAUGHT ME TO ASK. Volume and bioavailability were NOT AUTHORED and fell through to the solver defaults, while the correct scaling for the active metabolite is about a third — so bioavailability ran 2.7-fold high against a correspondingly small volume, and since only their RATIO reaches exposure the model landed within a quarter BY ACCIDENT. Both are now authored, the volume sitting inside an independent verbatim band of 23 to 60 L, with a verbatim absorption lag. The absorption rate and half-life were already verified verbatim from the correct tablet arm. A DIMENSIONAL CAVEAT TRAVELS WITH THE SOURCE: its abstract prints an exposure "1,269:1,338 mg.hour/ml", which is impossible as written; the numeral is verbatim and the UNIT in the abstract is a typo. MY PRIOR THAT THE MASS DEFECT PROPAGATES INTO THE OCCUPANCY ROWS IS REFUTED — both rows explicitly used the metabolite mass and their arithmetic is exact, so THE AUTHOR QUARANTINED IT CORRECTLY. BUT THE DEFECT IS LIVE SOMEWHERE ELSE ENTIRELY: the app attaches the record molecular weight to every ligand and back-converts the stored concentration for display, so the screen shows affinities several percent off what the sources say. That is a catalogue-wide convention question, logged rather than patched here. FINALLY, THE PROSE CONTRADICTS ITS OWN NUMBERS: it calls the drug COX-2-preferential while the stored pair is three-and-a-half-fold COX-1-selective. MASS: the stored weight was the parent while the declared analyte is the active metabolite. THE OCCUPANCY ROWS ALREADY USED THE CORRECT METABOLITE MASS IN THEIR OWN CONVERSIONS, so the stored value and the rows disagreed with each other — which is how the app came to display affinities several percent away from what the sources state.
Pharmacokinetics
- Oral — t½ 27.2 h · F 100% · ka 0.67 h⁻¹ · Vd 30.9 L
Sources: PMID:10377455, PMID:3687999, PMID:6526543, PMID:7781261