Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia
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’...
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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2022
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| Online Access: | https://hdl.handle.net/10171/64793 |
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| author | Azanza, J.R. (José Ramón) Sadaba, B. (Belén) Díez, N. (Nieves) |
| author_facet | Azanza, J.R. (José Ramón) Sadaba, B. (Belén) Díez, N. (Nieves) |
| author_sort | Azanza, J.R. (José Ramón) |
| collection | DSpace |
| description | 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. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-64793 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2022 |
| publisher | Graphy |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-647932022-12-12T06:07:11Z Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia Azanza, J.R. (José Ramón) Sadaba, B. (Belén) Díez, N. (Nieves) BCR/ABL tyrosine kinase inhibitor Bosutinib Ponatinib Imatinib Nilotinib Dasatinib Chronic myeloid leukemia Pharmacology 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. 2022-12-05T08:27:22Z 2022-12-05T08:27:22Z 2018 info:eu-repo/semantics/article https://hdl.handle.net/10171/64793 eng info:eu-repo/semantics/openAccess application/pdf Graphy |
| spellingShingle | BCR/ABL tyrosine kinase inhibitor Bosutinib Ponatinib Imatinib Nilotinib Dasatinib Chronic myeloid leukemia Pharmacology Azanza, J.R. (José Ramón) Sadaba, B. (Belén) Díez, N. (Nieves) Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia |
| title | Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia |
| title_full | Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia |
| title_fullStr | Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia |
| title_full_unstemmed | Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia |
| title_short | Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia |
| title_sort | comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia |
| topic | BCR/ABL tyrosine kinase inhibitor Bosutinib Ponatinib Imatinib Nilotinib Dasatinib Chronic myeloid leukemia Pharmacology |
| url | https://hdl.handle.net/10171/64793 |
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