Daprodustat
Daprodustat. A reversible inhibitor of the HIF prolyl-hydroxylases PH1, PH2 and PH3, stabilising HIF-1alpha and HIF-2alpha and raising… Oral half-life 1.9 h.
A reversible inhibitor of the HIF prolyl-hydroxylases PH1, PH2 and PH3, stabilising HIF-1alpha and HIF-2alpha and raising erythropoietin transcription. Jesduvroq label section 12.1 verbatim: "Daprodustat is a reversible inhibitor of HIF-PH1, PH2 and PH3 (IC50 in the low nM range). This activity results in the stabilization and nuclear accumulation of HIF-1alpha and HIF-2alpha transcription factors, leading to increased transcription of the HIF-responsive genes, including erythropoietin." The discovery paper calls it "a pyrimidinetrione-glycinamide low nanomolar inhibitor of PHDs 1-3" (PMID:28928122). BOTH SOURCES SAY "LOW NANOMOLAR" AND NEITHER PRINTS A NUMBER, so no occupancy row is authored.
PubChem CID 91617630 (C19H27N3O6, 393.4), re-queried 2026-09-26, and the Jesduvroq label section 11 agrees verbatim: "The molecular formula of daprodustat is C19H27N3O6, and its molecular mass is 393.43." No salt form exists (PUGREST.NotFound for "daprodustat sodium"), so doses are the free base. DOSES are the label's, section 2.3 Table 1 for dialysis patients not on an ESA, once daily: 4 mg at Hb below 9 g/dL, 2 mg at Hb 9-10, 1 mg above 10; section 11 lists 1, 2, 4, 6 and 8 mg tablets. THE LABEL'S OWN PK, recorded for cross-check and NOT averaged with the paper's: Vss 14.3 L (against the paper's 14.6), absolute F 65% (against 0.661), "Mean clearance from plasma was 18.9 L/h" (against 19.3), and a half-life given only as a RANGE, "approximately 1 hour to 4 hours" — the paper's measured 1.92 h sits inside it, which is why the paper is preferred. TWO SOURCES FOR EACH QUANTITY, NEVER MEANED. POPULATION PK, RECORDED NOT STORED: PMID:39259485 (707 CKD patients, titrated, steady state) gives "Oral clearance and volume of distribution was 24.6 L/h and 26.9 L" — both APPARENT, from a three-compartment fit that does not say whether 26.9 L is central or steady-state, so R15 bars it from this slot; and it must never be paired with the absolute F 0.661, which would divide by F twice. A DOSE THAT IS NOT THERAPEUTIC: PMID:29545948 uses 100 mg and says so — "100-mg daprodustat exceeds the planned top therapeutic dose" — that is a DDI probe dose and is not in the stored range.
Pharmacokinetics
- Oral — t½ 1.9 h · F 66% · Vd 53.46 L
Sources: PMID:34713596, PMID:28928122, PMID:39259485, PMID:37885335