DDInter1008 DDInter649
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
Enzalutamide is an androgen receptor (AR) inhibitor for the treatment of castration-resistant prostate cancer (CRPC), both metastatic and non-metastatic. It is a second-generation antiandrogen agent that the FDA approved on August 31, 2012.[L40639, A252667] Although androgen deprivation therapy (ADT) is the first-line treatment of prostate cancer and remission can be achieved, arising resistance is inevitable, becoming castration-resistant prostate cancer. Until recently, docetaxel is the only treatment available for metastatic CRPC; however, AR inhibitors have been developed for more targeted therapy, although first-generation AR inhibitors like bicalutamide did not substantially increase the survival rate. Second-generation such as enzalutamide is more efficacious due to a higher affinity to AR and no partial agonist activity compared to bicalutamide.[A252667,A252642] Due to a favorable pharmacological profile, a phase 1 study of enzalutamide was initiated in July 2007. Compared to the average time of 10 to 15 years for a drug to go from pre-clinical to clinical studies, enzalutamide was developed relatively rapidly.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Enzalutamide
Ketoconazole {u} (Compound) causes {v} (Side Effect) Pruritus
Pruritus {u} (Side Effect) is caused by {v} (Compound) Enzalutamide
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Enzalutamide
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Bicalutamide
Bicalutamide {u} (Compound) resembles {v} (Compound) Enzalutamide
Ketoconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Mirabegron
Mirabegron {u} may cause a minor interaction that can limit clinical effects when taken with {v} Enzalutamide
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Nilutamide
Nilutamide {u} (Compound) resembles {v} (Compound) Enzalutamide
Ketoconazole {u} (Compound) causes {v} (Side Effect) Pruritus
Pruritus {u} (Side Effect) is caused by {v} (Compound) Nilutamide
Nilutamide {u} (Compound) resembles {v} (Compound) Enzalutamide
Ketoconazole {u} (Compound) causes {v} (Side Effect) Unspecified disorder of skin and subcutaneous tissue
Unspecified disorder of skin and subcutaneous tissue {u} (Side Effect) is caused by {v} (Compound) Bicalutamide
Bicalutamide {u} (Compound) resembles {v} (Compound) Enzalutamide
Ketoconazole {u} (Compound) causes {v} (Side Effect) Connective tissue disorder
Connective tissue disorder {u} (Side Effect) is caused by {v} (Compound) Mirabegron
Mirabegron {u} may cause a minor interaction that can limit clinical effects when taken with {v} Enzalutamide
Ketoconazole {u} (Compound) resembles {v} (Compound) Itraconazole
Itraconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Enzalutamide
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Enzalutamide (Compound)
Ketoconazole (Compound) causes Pruritus (Side Effect) and Pruritus (Side Effect) is caused by Enzalutamide (Compound)
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Enzalutamide
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Bicalutamide (Compound) and Bicalutamide (Compound) resembles Enzalutamide (Compound)
Ketoconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Mirabegron (Compound) and Mirabegron may cause a minor interaction that can limit clinical effects when taken with Enzalutamide
Ketoconazole (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Nilutamide (Compound) and Nilutamide (Compound) resembles Enzalutamide (Compound)
Ketoconazole (Compound) causes Pruritus (Side Effect) and Pruritus (Side Effect) is caused by Nilutamide (Compound) and Nilutamide (Compound) resembles Enzalutamide (Compound)
Ketoconazole (Compound) causes Unspecified disorder of skin and subcutaneous tissue (Side Effect) and Unspecified disorder of skin and subcutaneous tissue (Side Effect) is caused by Bicalutamide (Compound) and Bicalutamide (Compound) resembles Enzalutamide (Compound)
Ketoconazole (Compound) causes Connective tissue disorder (Side Effect) and Connective tissue disorder (Side Effect) is caused by Mirabegron (Compound) and Mirabegron may cause a minor interaction that can limit clinical effects when taken with Enzalutamide
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Enzalutamide