DDInter1008 DDInter448
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
Crizotinib is a tyrosine kinase receptor inhibitor used for the treatment of anaplastic lymphoma kinase (ALK) or ROS1-positive non-small cell lung cancer (NSCLC) tumors, as well as ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT). By targeting the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein, crizotinib offers robust effectiveness in treating NSCLC in patients with this type of rearrangement. Crizotinib was the first-in-class drug used to treat ALK-positive tumors. Second- and third-generation ALK-tyrosine kinase-inhibitors have overcome many of the pharmacodynamic and genetic resistance mechanisms crizotinib is prone to. Crizotinib was approved by the FDA in 2011, and its use is accompanied by FDA-approved tests used to detect ALK and ROS1 rearrangements.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Crizotinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) MSMO1
MSMO1 {u} (Gene) is upregulated by {v} (Compound) Crizotinib
Ketoconazole {u} (Compound) binds {v} (Gene) and {u} (Compound) upregulates {v} (Gene) CYP51A1
CYP51A1 {u} (Gene) is upregulated by {v} (Compound) Crizotinib
Ketoconazole {u} (Compound) is included by {v} (Pharmacologic Class) P-Glycoprotein Inhibitors
P-Glycoprotein Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Crizotinib
Ketoconazole {u} (Compound) downregulates {v} (Gene) SLC35F2
SLC35F2 {u} (Gene) is downregulated by {v} (Compound) Crizotinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Fatigue
Fatigue {u} (Side Effect) is caused by {v} (Compound) Crizotinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Crizotinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) covaries with {v} (Gene) PTK2B
PTK2B {u} (Gene) is bound by {v} (Compound) Crizotinib
Ketoconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is associated with {v} (Disease) lung cancer
lung cancer {u} (Disease) is treated by {v} (Compound) Crizotinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A5
CYP3A5 {u} (Gene) regulates {v} (Gene) CDK7
CDK7 {u} (Gene) is bound by {v} (Compound) Crizotinib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Crizotinib (Compound)
Ketoconazole (Compound) upregulates MSMO1 (Gene) and MSMO1 (Gene) is upregulated by Crizotinib (Compound)
Ketoconazole (Compound) binds CYP51A1 (Gene) and Ketoconazole (Compound) upregulates CYP51A1 (Gene) and CYP51A1 (Gene) is upregulated by Crizotinib (Compound)
Ketoconazole (Compound) is included by P-Glycoprotein Inhibitors (Pharmacologic Class) and P-Glycoprotein Inhibitors (Pharmacologic Class) includes Crizotinib (Compound)
Ketoconazole (Compound) downregulates SLC35F2 (Gene) and SLC35F2 (Gene) is downregulated by Crizotinib (Compound)
Ketoconazole (Compound) causes Fatigue (Side Effect) and Fatigue (Side Effect) is caused by Crizotinib (Compound)
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Crizotinib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) covaries with PTK2B (Gene) and PTK2B (Gene) is bound by Crizotinib (Compound)
Ketoconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is associated with lung cancer (Disease) and lung cancer (Disease) is treated by Crizotinib (Compound)
Ketoconazole (Compound) binds CYP3A5 (Gene) and CYP3A5 (Gene) regulates CDK7 (Gene) and CDK7 (Gene) is bound by Crizotinib (Compound)