Dasatinib
Dasatinib. Multi-kinase inhibitor: BCR-ABL, SRC family, EPHA2, PDGFR, KIT. In oncology, treats Ph+ ALL + CML (imatinib-resistant). Recent research… Oral half-life 4 h.
Multi-kinase inhibitor: BCR-ABL, SRC family, EPHA2, PDGFR, KIT. In oncology, treats Ph+ ALL + CML (imatinib-resistant). Recent research interest as a senolytic — paired with quercetin, selectively clears senescent cells in preclinical + early human (IPF, diabetic kidney disease) trials.
PK: THE LARGEST EXPOSURE ERROR IN THIS BATCH — 18.5x — AND ITS OWN CITATION REFUTES THE CULPRIT. That paper states "The absolute bioavailability of dasatinib in humans is unknown due to the lack of an intravenous formulation preventing calculation of the reference exposure." So F 0.14 is not merely unsourced, it is contradicted, and there is a likely donor: a review covering this drug and pazopanib side by side says "Absolute bioavailability in humans has been investigated only for imatinib (almost 100%) and pazopanib (14-39%; n = 3)" — the LOWER ENDPOINT OF A DIFFERENT DRUG RANGE. AND THE VOLUME PROVES THE DOUBLE DIVISION ARITHMETICALLY: the label gives "The apparent volume of distribution is 2505 L" and "The mean apparent oral clearance is 363.8 L/hr", and 2100 x ln2/4 reproduces 363.9 — the label CL/F to four figures. Someone solved the volume from an APPARENT clearance and then applied F on top of it. Because no human intravenous dasatinib exists the volume cannot be anything but V/F, so this is class 6 with certainty rather than by inference, and F is pinned to 1. A 2.4x residual against an independent patient study remains and is the class-12 residue of a terminal-phase volume. A scalar F is fragile here regardless: absorption is pH-dependent.
Pharmacokinetics
- Oral — t½ 4 h · F 100% · ka 2.65 h⁻¹ · Vd 2100 L
Related compounds
- Quercetin — synergistic
Sources: PMID:32112275, PMID:27995880, PMID:21827214