Abstract
There are 5 BCR/ABL tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML): bosutinib, ponatinib, imatinib, nilotinib and dasatinib. The availability of several therapeutic options raises the possibility of individualizing patient treatment. When evaluating patients’ individual pharmacological profiles, it is important to take into account the differences in the chemical structures of the drugs. Bosutinib, which has a unique interaction and safety profile, is a quinazoline, unlike the other TKIs that have a pyrimidine structure. All 5 TKIs inhibit the BCR/ABL tyrosine kinase, although only ponatinib is active against the strains expressing the T315I mutation. In addition, the 5 TKIs are generally non-selective drugs that can also inhibit other tyrosine kinases, such as cKIT or PDGFR, leading to both benefits in the treatment of some gastrointestinal tumors as well as additional adverse events. These drugs are orally administered and show moderate bioavailability, a large volume of distribution, high protein binding, and elimination after intense metabolism involving various Cytochrome P450 (CYP). They are also substrates of transport proteins and interact with inducers and inhibitors. All TKIs, except bosutinib, can inhibit the activity of transport proteins, leading to important drug interactions. As such, bosutinib is the drug with the better pharmacological profile. There is a close relationship between drug concentration and the beneficial/toxic effects of imatinib, nilotinib, and dasatinib. Therefore, plasma levels should be monitored to optimize patient treatment. Currently, there is no information for ponatinib. Overall, there is a high incidence of adverse events; although these do not usually lead to treatment discontinuation. All 5 TKIs have a similar safety profile; however, each TKI has unique adverse events. Pharmacological differences can identify the drug that is best suited to each patient, helping optimize CML therapy.
Highlights
Chronic myeloid leukemia (CML) is a myeloproliferative disorder produced by clonal proliferation of multipotential hematopoietic cells
CML is characterized by the presence of the Philadelphia chromosome, due to a translocation between chromosomes 9 and 22 that forms a fusion gene of Breakpoint cluster region (BCR)/Abelson murine leukemia gene (ABL)[2]
There are 5 drugs for CML that act by inhibiting tyrosine kinases (TK) including, the ABL kinase, which is involved in the genesis of this disease
Summary
Chronic myeloid leukemia (CML) is a myeloproliferative disorder produced by clonal proliferation of multipotential hematopoietic cells. The first drug was imatinib, after which nilotinib, dasatinib, bosutinib, and ponatinib were developed. Resistance to imatinib and to other BCR/ABL inhibitors can occur because of infra therapeutic drug concentrations, due to lack of compliance by the patient, inadequate doses, alterations in the activity of the isoenzymes that metabolize the inhibitors, or alterations of the transporter proteins that are involved in the pharmacokinetic process [22,23,24,25].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: International Journal of Clinical Pharmacology & Pharmacotherapy
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
