DDInter1008 DDInter484
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
Dasatinib is an orally available multikinase inhibitor indicated for the treatment of Philadelphia chromosome (Ph)-positive leukemias.[A2224,L45171] Ph is a chromosomal abnormality found in patients with chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL), where the ABL tyrosine kinase and the breakpoint cluster region (BCR) gene transcribe the chimeric protein BCR-ABL. BCR-ABL is associated with the uncontrolled activity of the ABL tyrosine kinase and is involved in the pathogenesis of CML and 15-30% of ALL cases.[A11377,A33432] Dasatinib also inhibits a spectrum of kinases involved in cancer, including several SRC-family kinases. Unlike [imatinib], another tyrosine kinase used for the treatment of CML and Ph-positive ALL, dasatinib inhibits the active and inactive conformations of the ABL kinase domain.[A2226,A11377] Also, mutations in the kinase domain of BCR-ABL may lead to relapse during imatinib treatment. Since dasatinib does not interact with some of the residues involved in those mutations, the use of this drug represents a therapeutic alternative for patients with cancers that have developed imatinib-resistance. The use of dasatinib was first approved by the FDA in 2006.[L45171,L45186]
Ketoconazole {u} (Compound) binds {v} (Gene) CYP1B1
CYP1B1 {u} (Gene) is bound by {v} (Compound) Dasatinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) INSIG1
INSIG1 {u} (Gene) is upregulated by {v} (Compound) Dasatinib
Ketoconazole {u} (Compound) downregulates {v} (Gene) SLC35F2
SLC35F2 {u} (Gene) is downregulated by {v} (Compound) Dasatinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Body temperature increased
Body temperature increased {u} (Side Effect) is caused by {v} (Compound) Dasatinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Dasatinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP1B1
CYP1B1 {u} (Gene) is regulated by {v} (Gene) PPARGC1A
PPARGC1A {u} (Gene) is upregulated by {v} (Compound) Dasatinib
Ketoconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is associated with {v} (Disease) hematologic cancer
hematologic cancer {u} (Disease) is treated by {v} (Compound) Dasatinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) covaries with {v} (Gene) FMO3
FMO3 {u} (Gene) is bound by {v} (Compound) Dasatinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A5
CYP3A5 {u} (Gene) regulates {v} (Gene) HERC6
HERC6 {u} (Gene) is upregulated by {v} (Compound) Dasatinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP1A2
CYP1A2 {u} (Gene) is bound by {v} (Compound) Almotriptan
Almotriptan {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Dasatinib
Ketoconazole (Compound) binds CYP1B1 (Gene) and CYP1B1 (Gene) is bound by Dasatinib (Compound)
Ketoconazole (Compound) upregulates INSIG1 (Gene) and INSIG1 (Gene) is upregulated by Dasatinib (Compound)
Ketoconazole (Compound) downregulates SLC35F2 (Gene) and SLC35F2 (Gene) is downregulated by Dasatinib (Compound)
Ketoconazole (Compound) causes Body temperature increased (Side Effect) and Body temperature increased (Side Effect) is caused by Dasatinib (Compound)
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Dasatinib
Ketoconazole (Compound) binds CYP1B1 (Gene) and CYP1B1 (Gene) is regulated by PPARGC1A (Gene) and PPARGC1A (Gene) is upregulated by Dasatinib (Compound)
Ketoconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is associated with hematologic cancer (Disease) and hematologic cancer (Disease) is treated by Dasatinib (Compound)
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) covaries with FMO3 (Gene) and FMO3 (Gene) is bound by Dasatinib (Compound)
Ketoconazole (Compound) binds CYP3A5 (Gene) and CYP3A5 (Gene) regulates HERC6 (Gene) and HERC6 (Gene) is upregulated by Dasatinib (Compound)
Ketoconazole (Compound) binds CYP1A2 (Gene) and CYP1A2 (Gene) is bound by Almotriptan (Compound) and Almotriptan may cause a moderate interaction that could exacerbate diseases when taken with Dasatinib