Ruxolitinib
Ruxolitinib. JAK1/JAK2 inhibitor — first JAK inhibitor approved (2011). Indications: myelofibrosis, polycythemia vera (HU-resistant)… Oral half-life 3 h.
JAK1/JAK2 inhibitor — first JAK inhibitor approved (2011). Indications: myelofibrosis, polycythemia vera (HU-resistant), steroid-refractory acute + chronic GVHD. CYP3A4 substrate. Discontinuation of ruxolitinib in MF requires a slow taper to avoid cytokine-rebound systemic inflammatory response. PK (Jakafi label, 20 mg PO bid IR): Cmax 205-7100 nM across single-dose range (linear), Tmax 1-2 h, F ≥95%, t½ 3.0 h IR formulation (5.4 h newer ER once-daily formulation), Vss 72 L. CYP3A4 substrate; no significant food effect.
PK: VERIFIED, AND SAYING SO CLEARLY IS THE POINT. Every value is sourceable and the arithmetic lands at 1.1%: implied clearance 17.5 L/h against the label verbatim "Ruxolitinib clearance (%CV) was 17.7 L/h in women and 22.1 L/h in men with MF", independently corroborated by a population analysis giving "22.1 and 17.7 L/h for a typical male and female subject" and by the label own dose-ranging exposures. The volume is the label verbatim steady-state figure and the half-life is verbatim in three separate sources. A DIGIT COLLISION WAS AVAILABLE AND CHECKED: a population paper reports a "median weight of 72.9 kg" beside this record volume of 72 L, but the label figure is independent and the resemblance is coincidence. The two-compartment risk flagged in that review does not bite — the predicted peak is only 1.3-1.5x low, which is ordinary one-compartment behaviour rather than the structural failure seen elsewhere in this batch. Only the citation moves: the previously cited review supports the bioavailability but not the volume or half-life. One prose nit: the mechanism string says 5.4 h for the extended-release form where the label says approximately 5. PK: THE STORED ABSORPTION RATE WAS THE SOLVER DEFAULT WEARING A CITATION. A ka of 1.0/h is exactly what resolvePk substitutes when the field is ABSENT, and no source on this record states one. Removing it is NUMERICALLY A NO-OP — the resolver supplies the identical number — so no curve moves; what changes is that the record stops asserting an absorption rate it never measured. This is the same shape already found on a volume of 35 L, which is likewise the default at the seventy-kilogram reference. THE WIDER DEBT IS LEFT ALONE ON PURPOSE: twelve values account for 152 of the 276 authored absorption rates, but the other eleven are NOT the default, so deleting those would move their curves rather than leave them, which is the error this audit spent a batch documenting.
Pharmacokinetics
- Oral — t½ 3 h · F 95% · Vd 72 L
Sources: PMID:37000342, PMID:23677817