Febuxostat
Febuxostat. Non-purine xanthine oxidase inhibitor. More potent uric acid lowering than allopurinol. CARES trial (2018) showed CV mortality… Oral half-life 9.4 h.
Non-purine xanthine oxidase inhibitor. More potent uric acid lowering than allopurinol. CARES trial (2018) showed CV mortality signal vs allopurinol → black-box warning + reserved for allopurinol-intolerant patients.
PK: CLASS 12, AND THE LARGEST QUANTITATIVE ERROR IN ITS GROUP. ka 3.6 and V 32.8 are both verbatim - "the population mean for apparent clearance (CL/F), apparent central volume of distribution (Vc/F) ... and absorption rate constant (ka) ... were 6.91 l h-1, 32.8 l ... and 3.6 h-1" - but 32.8 L is the CENTRAL volume of a TWO-COMPARTMENT model and this registry runs one, so the stored set implied an AUC per dose of 0.259 h/L against a measured 0.095, OVER-PREDICTING EXPOSURE 2.7-FOLD. It is also explicitly apparent and sat beside an independent F 0.84, which is itself the label "at least 84% ABSORBED" - an absorption fraction read as a bioavailability. The volume becomes the one-compartment value that reproduces this drug own verbatim clearance at its own verbatim terminal half-life, "an apparent oral clearance (CL/F) of 10.5 +/- 3.4 L/h" and "the terminal t 1/2 determined at daily doses of 40 mg or more is 9.4 +/- 4.9 h", and that derivation is disclosed rather than presented as a measurement. The paper Vss/F of 48 L is NOT used, because a steady-state two-compartment volume is not a one-compartment volume either. F is pinned to 1 since every parameter here is apparent. ka 3.6 is the FASTED value: "Food reduced the relative biovailability and ka by 67% and 87%". MY THIN-LITERATURE PRIOR WAS RIGHT ONLY FOR F.
Pharmacokinetics
- Oral — t½ 9.4 h · F 100% · ka 3.6 h⁻¹ · Vd 142 L
Sources: PMID:35849446, PMID:8243554, PMID:27753003