|Drug class||Tyrosine kinase inhibitor|
|Main uses||Chronic myelogenous leukemia (CML)|
|Side effects||Diarrhea, rash, nausea, tiredness, liver problems, respiratory tract infection, fever, headache|
|Metabolism||By CYP3A4, to inactive metabolites|
|Elimination half-life||22.5±1.7 hours|
|Excretion||Foecal (91.3%) and renal (3%)|
|Chemical and physical data|
|Molar mass||530.45 g·mol−1|
|3D model (JSmol)|
Bosutinib codenamed SKI-606, marketed under the trade name Bosulif, is a medication used to treat chronic myelogenous leukemia (CML). Specifically it is used for cases that are Philadelphia chromosome positive. It is taken by mouth.
Common side effects include diarrhea, rash, nausea, tiredness, liver problems, respiratory tract infection, fever, and headache. Other side effects may include bone marrow suppression, heart damage, swelling, and kidney problems. Use in pregnancy may harm the baby. It is a tyrosine kinase inhibitor that blocks BCR-ABL and src.
Bosutinib was approved for medical use in the United States in 2012 and Europe in 2013. In the United Kingdom 4 weeks of treatment costs the NHS about £3,400 as of 2021. This amount in the United States is about 17,000 USD.
Bosutinib received US FDA and EU European Medicines Agency approval in September 2012, and March 2013, respectively for the treatment of adults with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.
It is generally started at a dose of 400 to 500 mg per day, though may be increased to 600 mg per day.
Bosutinib is both a substrate and an inhibitor of P-glycoprotein (P-gp) and CYP3A4. Hence P-gp and CYP3A4 inhibitors may increase plasma levels of bosutinib. Likewise CYP3A4 inducers may reduce plasma concentrations of bosutinib. It may also alter the metabolism and uptake (into the GIT by means of its P-gp inhibitory effects) of other drugs that are substrates for P-gp and CYP3A4.
It is an ATP-competitive Bcr-Abl tyrosine-kinase inhibitor with an additional inhibitory effect on Src family kinases (including Src, Lyn and Hck). It has also shown activity against the receptors for platelet derived growth factor and vascular endothelial growth factor. Bosutinib inhibited 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid cell lines, but did not inhibit T315I and V299L mutant cells.
Bosutinib is metabolized through CYP3A4.
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