Vadadustat
Vadadustat. A reversible inhibitor of HIF prolyl-4-hydroxylases PH1, PH2 and PH3. Vafseo label section 12.1 verbatim: "Vadadustat is a… Oral half-life 5.8 h.
A reversible inhibitor of HIF prolyl-4-hydroxylases PH1, PH2 and PH3. Vafseo label section 12.1 verbatim: "Vadadustat is a reversible inhibitor of HIF-prolyl-4-hydroxylases (PH)1, PH2, and PH3 (IC50 in the nM range). This activity results in the stabilization and nuclear accumulation of HIF-1alpha and HIF-2alpha transcription factors, and increased production of erythropoietin (EPO)." Its preclinical characterisation adds the kinetics of inhibition, verbatim (vadadustat the subject, PMID:35926869): "PHD enzyme inhibition by vadadustat is competitive with endogenous cofactor 2-oxoglutarate and is insensitive to free iron concentration." THAT PAPER SAYS ONLY "similar low nanomolar inhibitory constant values" AND PRINTS NO NUMBER, so no occupancy row is authored.
PubChem CID 23634441 (C14H11ClN2O4, 306.70), re-queried 2026-09-26, matching the Vafseo label section 11 verbatim: "weight of 306.70. The empirical formula is C14H11ClN2O4." No salt form exists (PUGREST.NotFound for "vadadustat sodium"), so doses are the free acid. DOSES from the label: section 2.3, "The recommended starting dose is 300 mg orally once daily"; section 3 lists 150 mg, 300 mg and 450 mg film-coated tablets. FOUR POPULATIONS, FOUR HALF-LIVES, and mixing them is the trap this record is built to prevent: 4.5 h in healthy men (PMID:38924087, hedged, single-or-multiple); 5.8 h normal hepatic function at 450 mg single dose (PMID:33661566, stored); 7.2 h in CKD stage 3 and 8.5 h in CKD stage 4 after a single 500 mg dose, which are two populations and not a range (PMID:38924087); and from the label, "The mean half-life of vadadustat in patients on chronic hemodialysis was 13.9 hours" — nearly 3x the healthy figure and belonging to dialysis patients alone. AN UNREAD CORRECTION: PMID:38924087 has an erratum, PMID:39520093, whose own abstract carries no content, so what was corrected is unknown. That is the reason its 4.5 h is recorded here rather than stored. NO V, F, CL, Cmax OR AUC IS PUBLISHED ANYWHERE REACHED — absent from label section 12.3 and from every abstract fetched, and PMID:38924087 has no PMC copy, so its PK table is unread: full text NOT RETRIEVED, not silent.
Pharmacokinetics
- Oral — t½ 5.8 h · F 100%
Sources: PMID:33661566, PMID:35926869, PMID:38924087, PMID:39520093