Clinical Pharmacokinetics and Pharmacodynamics of Bosutinib

• Published in: Clinical pharmacokinetics Vol. 55; no. 10; pp. 1191 - 1204
• Main Authors: Abbas, Richat, Hsyu, Poe-Hirr
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2016; Springer Nature B.V
• Subjects: Aniline Compounds - pharmacokinetics; Aniline Compounds - pharmacology; Aniline Compounds - therapeutic use; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Area Under Curve; Asian Continental Ancestry Group; Clinical Trials as Topic; Cytochrome P-450 CYP3A - metabolism; Dose-Response Relationship, Drug; Drug Interactions; Electrocardiography; Half-Life; Humans; Internal Medicine; Intestinal Absorption; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Liver Failure - metabolism; Medicine; Medicine & Public Health; Metabolic Clearance Rate; Nitriles - pharmacokinetics; Nitriles - pharmacology; Nitriles - therapeutic use; Pharmacology/Toxicology; Pharmacotherapy; Protein Binding; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - pharmacology; Quinolines - pharmacokinetics; Quinolines - pharmacology; Quinolines - therapeutic use; Renal Insufficiency - metabolism; Review Article; Imatinib; Chronic Myeloid Leukemia; Dabigatran; Ketoconazole; Lansoprazole
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.1007/s40262-016-0391-6

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.