DDInter1008 DDInter133
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
Atorvastatin (Lipitor®), is a lipid-lowering drug included in the statin class of medications. By inhibiting the endogenous production of cholesterol in the liver, statins lower abnormal cholesterol and lipid levels, and ultimately reduce the risk of cardiovascular disease. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid. This conversion is a critical metabolic reaction involved in the production of several compounds involved in lipid metabolism and transport, including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as "bad cholesterol"), and very-low-density lipoprotein (VLDL). Prescribing statins is considered standard practice for patients following any cardiovascular event, and for people who are at moderate to high risk of developing cardiovascular disease. The evidence supporting statin use, coupled with minimal side effects and long term benefits, has resulted in wide use of this medication in North America.[A181087, A181406] Atorvastatin and other statins including [lovastatin], [pravastatin], [rosuvastatin], [fluvastatin], and [simvastatin] are considered first-line treatment options for dyslipidemia.[A181087, A181406] The increasing use of this class of drugs is largely attributed to the rise in cardiovascular diseases (CVD) (such as heart attack, atherosclerosis, angina, peripheral artery disease, and stroke) in many countries. An elevated cholesterol level (elevated low-density lipoprotein (LDL) levels in particular) is a significant risk factor for the development of CVD.[A181087,A181553] Several landmark studies demonstrate that the use of statins is associated with both a reduction in LDL levels and CVD risk.[A181090,A181093,A181096,A181427,A181475,A181538] Statins were shown to reduce the incidences of all-cause mortality, including fatal and non-fatal CVD, as well as the need for surgical revascularization or angioplasty following a heart attack.[A181087, A181406] Some evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within five years) statin use leads to a 20%-22% relative reduction in the number of major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.[A181397, A181403] Atorvastatin was first synthesized in 1985 by Dr. Bruce Roth and approved by the FDA in 1996. It is a pentasubstituted pyrrole formed by two contrasting moieties with an achiral heterocyclic core unit and a 3,5-dihydroxypentanoyl side chain identical to its parent compound. Unlike other members of the statin group, atorvastatin is an active compound and therefore does not require activation.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2D6
CYP2D6 {u} (Gene) is bound by {v} (Compound) Atorvastatin
Ketoconazole {u} (Compound) upregulates {v} (Gene) HMGCR
HMGCR {u} (Gene) is bound by {v} (Compound) Atorvastatin
Ketoconazole {u} (Compound) upregulates {v} (Gene) DDIT4
DDIT4 {u} (Gene) is upregulated by {v} (Compound) Atorvastatin
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2D6
CYP2D6 {u} (Gene) is bound by {v} (Compound) Fluvastatin
Fluvastatin {u} (Compound) resembles {v} (Compound) Atorvastatin
Ketoconazole {u} (Compound) binds {v} (Gene) SLCO1A2
SLCO1A2 {u} (Gene) is bound by {v} (Compound) Simvastatin
Simvastatin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Atorvastatin
Ketoconazole {u} (Compound) upregulates {v} (Gene) HMGCR
HMGCR {u} (Gene) is bound by {v} (Compound) and {u} (Gene) is upregulated by {v} (Compound) Pitavastatin
Pitavastatin {u} (Compound) resembles {v} (Compound) Atorvastatin
Ketoconazole {u} (Compound) resembles {v} (Compound) Itraconazole
Itraconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Atorvastatin
Ketoconazole {u} (Compound) upregulates {v} (Gene) DDIT4
DDIT4 {u} (Gene) is upregulated by {v} (Compound) Fluvastatin
Fluvastatin {u} (Compound) resembles {v} (Compound) Atorvastatin
Ketoconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) regulates {v} (Gene) PCNA
PCNA {u} (Gene) is downregulated by {v} (Compound) Atorvastatin
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C19
CYP2C19 {u} (Gene) is associated with {v} (Disease) coronary artery disease
coronary artery disease {u} (Disease) is treated by {v} (Compound) Atorvastatin
Ketoconazole (Compound) binds CYP2D6 (Gene) and CYP2D6 (Gene) is bound by Atorvastatin (Compound)
Ketoconazole (Compound) upregulates HMGCR (Gene) and HMGCR (Gene) is bound by Atorvastatin (Compound)
Ketoconazole (Compound) upregulates DDIT4 (Gene) and DDIT4 (Gene) is upregulated by Atorvastatin (Compound)
Ketoconazole (Compound) binds CYP2D6 (Gene) and CYP2D6 (Gene) is bound by Fluvastatin (Compound) and Fluvastatin (Compound) resembles Atorvastatin (Compound)
Ketoconazole (Compound) binds SLCO1A2 (Gene) and SLCO1A2 (Gene) is bound by Simvastatin (Compound) and Simvastatin may cause a moderate interaction that could exacerbate diseases when taken with Atorvastatin
Ketoconazole (Compound) upregulates HMGCR (Gene) and HMGCR (Gene) is bound by Pitavastatin (Compound) and HMGCR (Gene) is upregulated by Pitavastatin (Compound) and Pitavastatin (Compound) resembles Atorvastatin (Compound)
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Atorvastatin (Compound)
Ketoconazole (Compound) upregulates DDIT4 (Gene) and DDIT4 (Gene) is upregulated by Fluvastatin (Compound) and Fluvastatin (Compound) resembles Atorvastatin (Compound)
Ketoconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) regulates PCNA (Gene) and PCNA (Gene) is downregulated by Atorvastatin (Compound)
Ketoconazole (Compound) binds CYP2C19 (Gene) and CYP2C19 (Gene) is associated with coronary artery disease (Disease) and coronary artery disease (Disease) is treated by Atorvastatin (Compound)