DDInter1008 DDInter224
Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections.[FDA Label] It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus.[A181802,T116] Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981. At this time it was considered a significant improvement over previous antifungals, [miconazole] and [clotrimazole], due to its broad spectrum and good absorption. However, it was discovered that ketoconazole produces frequent gastrointestinal side effects and dose-related hepatitis.[A188054,A188057] These effects combined with waning efficacy led to its eventual replacement by triazole agents, [fluconazole], [itraconazole], [voriconazole], and [posaconazole]. Ketoconazole and its predecessor [clotrimazole] continue
Bosutinib is a 7-alkoxy-3-quinolinecarbonitrile that functions as a potent, dual SRC and ABL tyrosine kinase inhibitor indicated for chronic myelogenous leukemia (CML), specifically Philadelphia chromosome-positive (Ph+) CML. Philadelphia chromosome is a hallmark of CML due to the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR-ABL fusion protein.[A6902,A261796,A261801] The first BCR-ABL inhibitor, [imatinib], was introduced over a decade ago as a breakthrough in CML management; however, emerging resistance to [imatinib] poses challenges in achieving remission. Second-generation BCR-ABL inhibitors like bosutinib inhibit most resistance-conferring BCR-ABL mutations except V299L and T315, thus providing more therapeutic options for patients.[A6901,A17961] Bosutinib was first approved by the FDA in 2012 for the treatment of adult chronic, accelerated, or blast-phase Ph+ CML with resistance or intolerance to prior therapy. On September 26, 2023, bosutinib was also approved by the FDA for the treatment of pediatric CML that is newly diagnosed or resistant/intolerant to prior therapy. This approval was based on favorable results obtained from the open-label, randomized, multicenter trial BFORE that showed a significant improvement in major molecular response, defined as a ≤0.1% BCR ABL ratio on an international scale, with bosutinib treatment.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Bosutinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) INSIG1
INSIG1 {u} (Gene) is upregulated by {v} (Compound) Bosutinib
Ketoconazole {u} (Compound) binds {v} (Gene) and {u} (Compound) upregulates {v} (Gene) CYP51A1
CYP51A1 {u} (Gene) is upregulated by {v} (Compound) Bosutinib
Ketoconazole {u} (Compound) is included by {v} (Pharmacologic Class) P-Glycoprotein Inhibitors
P-Glycoprotein Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Bosutinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Decreased appetite
Decreased appetite {u} (Side Effect) is caused by {v} (Compound) Bosutinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Bosutinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Gefitinib
Gefitinib {u} (Compound) resembles {v} (Compound) Bosutinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) INSIG1
INSIG1 {u} (Gene) is regulated by {v} (Gene) HCK
HCK {u} (Gene) is bound by {v} (Compound) Bosutinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) FDFT1
FDFT1 {u} (Gene) regulates {v} (Gene) PTK2B
PTK2B {u} (Gene) is bound by {v} (Compound) Bosutinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) IDI1
IDI1 {u} (Gene) is regulated by {v} (Gene) SREBF2
SREBF2 {u} (Gene) is upregulated by {v} (Compound) Bosutinib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Bosutinib (Compound)
Ketoconazole (Compound) upregulates INSIG1 (Gene) and INSIG1 (Gene) is upregulated by Bosutinib (Compound)
Ketoconazole (Compound) binds CYP51A1 (Gene) and Ketoconazole (Compound) upregulates CYP51A1 (Gene) and CYP51A1 (Gene) is upregulated by Bosutinib (Compound)
Ketoconazole (Compound) is included by P-Glycoprotein Inhibitors (Pharmacologic Class) and P-Glycoprotein Inhibitors (Pharmacologic Class) includes Bosutinib (Compound)
Ketoconazole (Compound) causes Decreased appetite (Side Effect) and Decreased appetite (Side Effect) is caused by Bosutinib (Compound)
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Bosutinib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Gefitinib (Compound) and Gefitinib (Compound) resembles Bosutinib (Compound)
Ketoconazole (Compound) upregulates INSIG1 (Gene) and INSIG1 (Gene) is regulated by HCK (Gene) and HCK (Gene) is bound by Bosutinib (Compound)
Ketoconazole (Compound) upregulates FDFT1 (Gene) and FDFT1 (Gene) regulates PTK2B (Gene) and PTK2B (Gene) is bound by Bosutinib (Compound)
Ketoconazole (Compound) upregulates IDI1 (Gene) and IDI1 (Gene) is regulated by SREBF2 (Gene) and SREBF2 (Gene) is upregulated by Bosutinib (Compound)