DDInter458 DDInter1622
Cyclosporine is a calcineurin inhibitor known for its immunomodulatory properties that prevent organ transplant rejection and treat various inflammatory and autoimmune conditions. It is isolated from the fungus _Beauveria nivea_. Initially manufactured by Sandoz and approved for use by the FDA in 1983, cyclosporine is now available in various products by Novartis (previously known as Sandoz).[L11097,L3734,L11118]
Rosuvastatin, also known as the brand name product Crestor, is a lipid-lowering drug that belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage elevated lipid levels by inhibiting the endogenous production of cholesterol in the liver. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions 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 of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.[A181087, A181406] Rosuvastatin and other drugs from the statin class of medications including [atorvastatin], [pravastatin], [simvastatin], [fluvastatin], and [lovastatin] are considered first-line options for the treatment of dyslipidemia.[A181087, A181406] This is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world. Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.[A181087,A181553] Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.[A181090,A181093,A181096,A181427,A181475,A181538] Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing 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] Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in 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] While all statin medications are considered equally effective from a clinical standpoint, rosuvastatin is considered the most potent; doses of 10 to 40mg rosuvastatin per day were found in clinical studies to result in a 45.8% to 54.6% decreases in LDL cholesterol levels, which is about three-fold more potent than [atorvastatin]'s effects on LDL cholesterol.[A181409,A1793] However, the results of the SATURN trial concluded that despite this difference in potency, there was no difference in their effect on the progression of coronary atherosclerosis. Rosuvastatin is also a unique member of the class of statins due to its high hydrophilicity which increases hepatic uptake at the site of action, low bioavailability, and minimal metabolism via the Cytochrome P450 system. This last point results in less risk of drug-drug interactions compared to [atorvastatin], [lovastatin], and [simvastatin], which are all extensively metabolized by Cytochrome P450 (CYP) 3A4, an enzyme involved in the metabolism of many commonly used drugs. Drugs such as [ciclosporin], [gemfibrozil], and some antiretrovirals are more likely to interact with this statin through antagonism of OATP1B1 organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin.[F4649, F4652]
Cyclosporine {u} (Compound) binds {v} (Gene) ABCC1
ABCC1 {u} (Gene) is bound by {v} (Compound) Rosuvastatin
Cyclosporine {u} (Compound) upregulates {v} (Gene) SLC7A11
SLC7A11 {u} (Gene) is bound by {v} (Compound) Rosuvastatin
Cyclosporine {u} (Compound) downregulates {v} (Gene) CDC25B
CDC25B {u} (Gene) is upregulated by {v} (Compound) Rosuvastatin
Cyclosporine {u} (Compound) upregulates {v} (Gene) TSC22D3
TSC22D3 {u} (Gene) is upregulated by {v} (Compound) Rosuvastatin
Cyclosporine {u} (Compound) downregulates {v} (Gene) CDC20
CDC20 {u} (Gene) is downregulated by {v} (Compound) Rosuvastatin
Cyclosporine {u} (Compound) upregulates {v} (Gene) MYC
MYC {u} (Gene) is downregulated by {v} (Compound) Rosuvastatin
Cyclosporine {u} (Compound) causes {v} (Side Effect) Breast disorder
Breast disorder {u} (Side Effect) is caused by {v} (Compound) Rosuvastatin
Cyclosporine {u} (Compound) binds {v} (Gene) ABCC1
ABCC1 {u} (Gene) is bound by {v} (Compound) Atorvastatin
Atorvastatin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Rosuvastatin
Cyclosporine {u} (Compound) upregulates {v} (Gene) SLC7A11
SLC7A11 {u} (Gene) regulates {v} (Gene) VAT1
VAT1 {u} (Gene) is upregulated by {v} (Compound) Rosuvastatin
Cyclosporine {u} (Compound) binds {v} (Gene) ABCG2
ABCG2 {u} (Gene) regulates {v} (Gene) HDAC2
HDAC2 {u} (Gene) is downregulated by {v} (Compound) Rosuvastatin
Cyclosporine (Compound) binds ABCC1 (Gene) and ABCC1 (Gene) is bound by Rosuvastatin (Compound)
Cyclosporine (Compound) upregulates SLC7A11 (Gene) and SLC7A11 (Gene) is bound by Rosuvastatin (Compound)
Cyclosporine (Compound) downregulates CDC25B (Gene) and CDC25B (Gene) is upregulated by Rosuvastatin (Compound)
Cyclosporine (Compound) upregulates TSC22D3 (Gene) and TSC22D3 (Gene) is upregulated by Rosuvastatin (Compound)
Cyclosporine (Compound) downregulates CDC20 (Gene) and CDC20 (Gene) is downregulated by Rosuvastatin (Compound)
Cyclosporine (Compound) upregulates MYC (Gene) and MYC (Gene) is downregulated by Rosuvastatin (Compound)
Cyclosporine (Compound) causes Breast disorder (Side Effect) and Breast disorder (Side Effect) is caused by Rosuvastatin (Compound)
Cyclosporine (Compound) binds ABCC1 (Gene) and ABCC1 (Gene) is bound by Atorvastatin (Compound) and Atorvastatin may cause a moderate interaction that could exacerbate diseases when taken with Rosuvastatin
Cyclosporine (Compound) upregulates SLC7A11 (Gene) and SLC7A11 (Gene) regulates VAT1 (Gene) and VAT1 (Gene) is upregulated by Rosuvastatin (Compound)
Cyclosporine (Compound) binds ABCG2 (Gene) and ABCG2 (Gene) regulates HDAC2 (Gene) and HDAC2 (Gene) is downregulated by Rosuvastatin (Compound)