Clinical Pharmacokinetics and Pharmacodynamics of Bosutinib
| Autor: | Richat Abbas, Poe-Hirr Hsyu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Metabolic Clearance Rate Antineoplastic Agents Pharmacology Biology Intestinal absorption Electrocardiography 03 medical and health sciences 0302 clinical medicine Asian People Pharmacokinetics Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Nitriles medicine Cytochrome P-450 CYP3A Humans Drug Interactions Pharmacology (medical) Renal Insufficiency Protein Kinase Inhibitors Clinical Trials as Topic Aniline Compounds Dose-Response Relationship Drug CYP3A4 Myeloid leukemia medicine.disease Leukemia 030104 developmental biology Intestinal Absorption Area Under Curve 030220 oncology & carcinogenesis Pharmacodynamics Quinolines Bosutinib Liver Failure Half-Life Protein Binding medicine.drug Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Clinical Pharmacokinetics. 55:1191-1204 |
| ISSN: | 1179-1926 0312-5963 |
| DOI: | 10.1007/s40262-016-0391-6 |
| Popis: | Chronic myeloid leukemia (CML) is a clonal myeloproliferative stem cell disorder. Bosutinib is an oral, once-daily SRC/ABL tyrosine kinase inhibitor with very potent inhibitory activity. Bosutinib is effective against all phases of intolerant or resistant Philadelphia chromosome–positive CML that do not harbor the T315I or V299LABL kinase domain mutations. Peak plasma concentrations of bosutinib occur at 4–6 h following oral administration, and dose-proportional increases in exposure are observed at doses ranging from 200 to 800 mg. Absorption of bosutinib increases with food. Bosutinib is distributed extensively into the tissues. It is highly plasma protein bound (94 %) and is primarily metabolized in the liver by cytochrome P450 3A4. Bosutinib is well tolerated overall and has a unique but manageable toxicity profile. This article provides a review of the available clinical pharmacokinetic, pharmacodynamic, and drug–drug interaction data on bosutinib in healthy subjects, patients with CML, and special populations. |
| Databáze: | OpenAIRE |
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