bosutinib + ketoconazole

Bosutinib + ketoconazole is a combination of two drugs: bosutinib, a second-generation small molecule tyrosine kinase inhibitor primarily targeting BCR-ABL and Src-family kinases, and ketoconazole, a potent inhibitor of CYP3A4. Bosutinib is indicated for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), while ketoconazole is used here specifically to inhibit the CYP3A4 metabolism of bosutinib, resulting in significantly increased plasma concentrations of bosutinib. This interaction increases exposure to bosutinib (Cmax by ~5.2-fold, AUC by ~8.6-fold), decreases its clearance, and prolongs its half-life. The combination is not a therapeutically indicated regimen but is used experimentally to evaluate high exposure (supratherapeutic) pharmacokinetics and safety in healthy volunteers or pharmacokinetic studies[1][2][4][5].