Sorafenib
Sorafenib. Multi-kinase inhibitor — BRAF, VEGFR, PDGFR, c-Kit, FLT3, RET. Used for hepatocellular carcinoma + advanced renal cell carcinoma +… Oral half-life 18 h.
Multi-kinase inhibitor — BRAF, VEGFR, PDGFR, c-Kit, FLT3, RET. Used for hepatocellular carcinoma + advanced renal cell carcinoma + radioactive-iodine refractory thyroid cancer. Hand-foot skin reaction + hypertension common.
PK: F 0.4 IS THE DOSE. Its sole citation is a phase II efficacy trial in prostate cancer whose regimen is "a dose of 400 mg orally twice daily", and that paper supports none of the four stored values, reporting only exposure, peak concentration and a time-to-peak range. NO ABSOLUTE BIOAVAILABILITY CAN EXIST: there is no intravenous sorafenib and the literature states that these agents "have an unknown absolute bioavailability", so F is pinned to 1 and the volume stored as the published apparent 213 L. A FIXED BIOAVAILABILITY IS WRONG IN KIND HERE, not merely unsourced: "Absolute bioavailability significantly dropped with increasing daily doses of sorafenib", exposure rising only 47.3 to 75.9 across a fourfold dose range. So is a single absorption rate: the population model uses "four transit absorption compartments and enterohepatic circulation", with half the drug recycling and gall-bladder emptying near 6 h. The half-life of 18.2 h is DERIVED from that model own clearance and volume and is flagged as such, because no abstract states a sorafenib half-life at all.
Pharmacokinetics
- Oral — t½ 18.2 h · F 100% · Vd 213 L
Sources: PMID:18172272, PMID:21392074, PMID:19733976