ROSUVASTATIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H28FN3O6S
Molecular Weight	481.538
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C1=NC(=NC(C2=CC=C(F)C=C2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)N(C)S(C)(=O)=O

InChI

InChIKey=BPRHUIZQVSMCRT-VEUZHWNKSA-N

InChI=1S/C22H28FN3O6S/c1-13(2)20-18(10-9-16(27)11-17(28)12-19(29)30)21(14-5-7-15(23)8-6-14)25-22(24-20)26(3)33(4,31)32/h5-10,13,16-17,27-28H,11-12H2,1-4H3,(H,29,30)/b10-9+/t16-,17-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://adis.springer.com/drugs/800008548 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021366s016lbl.pdf

CRESTOR (rosuvastatin calcium) is an inhibitor of HMG-CoA reductase. It has been widely launched for the treatment of patients with dyslipidaemia and has also been approved in the US and EU to slow the progression of atherosclerosis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021366s016lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Dyslipidemia 30 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021366s016lbl.pdf	Primary	Approved 8429	CRESTOR Approved Use CRESTOR is an HMG Co-A reductase inhibitor indicated for: ••patients with primary hyperlipidemia and mixed dyslipidemia as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C (1.1) ••patients with hypertriglyceridemia as an adjunct to diet (1.2) ••patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet (1.3) ••patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB (1.4) ••slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to diet (1.5) ••pediatric patients 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy (1.1) ••risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors (1.6) Limitations of use (1.7): ••CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. 1.1 Hyperlipidemia and Mixed Dyslipidemia CRESTOR is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, nonHDL-C, and triglycerides and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and nonpharmacological interventions alone has been inadequate. Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH) Adjunct to diet to reduce Total-C, LDL-C and ApoB levels in adolescent boys and girls, who are at least one year post-menarche, 10-17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C > 190 mg/dL or > 160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors. 1.2 Hypertriglyceridemia CRESTOR is indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. 1.3 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) CRESTOR is indicated as an adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia). 1.4 Homozygous Familial Hypercholesterolemia CRESTOR is indicated as adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL-C, Total-C, and ApoB in adult patients with homozygous familial hypercholesterolemia. 1.5 Slowing of the Progression of Atherosclerosis CRESTOR is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels. 1.6 Primary Prevention of Cardiovascular Disease In individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age ≥ 50 years old in men and ≥ 60 years old in women, hsCRP ≥ 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, CRESTOR is indicated to: ••reduce the risk of stroke ••reduce the risk of myocardial infarction ••reduce the risk of arterial revascularization procedures 1.7 Limitations of Use CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. Launch Date 2003
Hypertriglyceridemia 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021366s016lbl.pdf	Primary	Approved 8429	CRESTOR Approved Use CRESTOR is an HMG Co-A reductase inhibitor indicated for: ••patients with primary hyperlipidemia and mixed dyslipidemia as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C (1.1) ••patients with hypertriglyceridemia as an adjunct to diet (1.2) ••patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet (1.3) ••patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB (1.4) ••slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to diet (1.5) ••pediatric patients 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy (1.1) ••risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors (1.6) Limitations of use (1.7): ••CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. 1.1 Hyperlipidemia and Mixed Dyslipidemia CRESTOR is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, nonHDL-C, and triglycerides and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and nonpharmacological interventions alone has been inadequate. Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH) Adjunct to diet to reduce Total-C, LDL-C and ApoB levels in adolescent boys and girls, who are at least one year post-menarche, 10-17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C > 190 mg/dL or > 160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors. 1.2 Hypertriglyceridemia CRESTOR is indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. 1.3 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) CRESTOR is indicated as an adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia). 1.4 Homozygous Familial Hypercholesterolemia CRESTOR is indicated as adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL-C, Total-C, and ApoB in adult patients with homozygous familial hypercholesterolemia. 1.5 Slowing of the Progression of Atherosclerosis CRESTOR is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels. 1.6 Primary Prevention of Cardiovascular Disease In individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age ≥ 50 years old in men and ≥ 60 years old in women, hsCRP ≥ 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, CRESTOR is indicated to: ••reduce the risk of stroke ••reduce the risk of myocardial infarction ••reduce the risk of arterial revascularization procedures 1.7 Limitations of Use CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. Launch Date 2003
Dysbetalipoproteinemia 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021366s016lbl.pdf	Primary	Approved 8429	CRESTOR Approved Use CRESTOR is an HMG Co-A reductase inhibitor indicated for: ••patients with primary hyperlipidemia and mixed dyslipidemia as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C (1.1) ••patients with hypertriglyceridemia as an adjunct to diet (1.2) ••patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet (1.3) ••patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB (1.4) ••slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to diet (1.5) ••pediatric patients 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy (1.1) ••risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors (1.6) Limitations of use (1.7): ••CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. 1.1 Hyperlipidemia and Mixed Dyslipidemia CRESTOR is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, nonHDL-C, and triglycerides and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and nonpharmacological interventions alone has been inadequate. Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH) Adjunct to diet to reduce Total-C, LDL-C and ApoB levels in adolescent boys and girls, who are at least one year post-menarche, 10-17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C > 190 mg/dL or > 160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors. 1.2 Hypertriglyceridemia CRESTOR is indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. 1.3 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) CRESTOR is indicated as an adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia). 1.4 Homozygous Familial Hypercholesterolemia CRESTOR is indicated as adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL-C, Total-C, and ApoB in adult patients with homozygous familial hypercholesterolemia. 1.5 Slowing of the Progression of Atherosclerosis CRESTOR is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels. 1.6 Primary Prevention of Cardiovascular Disease In individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age ≥ 50 years old in men and ≥ 60 years old in women, hsCRP ≥ 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, CRESTOR is indicated to: ••reduce the risk of stroke ••reduce the risk of myocardial infarction ••reduce the risk of arterial revascularization procedures 1.7 Limitations of Use CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. Launch Date 2003
Hypercholesterolemia 47 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021366s016lbl.pdf	Primary	Approved 8429	CRESTOR Approved Use CRESTOR is an HMG Co-A reductase inhibitor indicated for: ••patients with primary hyperlipidemia and mixed dyslipidemia as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C (1.1) ••patients with hypertriglyceridemia as an adjunct to diet (1.2) ••patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet (1.3) ••patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB (1.4) ••slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to diet (1.5) ••pediatric patients 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy (1.1) ••risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors (1.6) Limitations of use (1.7): ••CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. 1.1 Hyperlipidemia and Mixed Dyslipidemia CRESTOR is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, nonHDL-C, and triglycerides and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and nonpharmacological interventions alone has been inadequate. Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH) Adjunct to diet to reduce Total-C, LDL-C and ApoB levels in adolescent boys and girls, who are at least one year post-menarche, 10-17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C > 190 mg/dL or > 160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors. 1.2 Hypertriglyceridemia CRESTOR is indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. 1.3 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) CRESTOR is indicated as an adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia). 1.4 Homozygous Familial Hypercholesterolemia CRESTOR is indicated as adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL-C, Total-C, and ApoB in adult patients with homozygous familial hypercholesterolemia. 1.5 Slowing of the Progression of Atherosclerosis CRESTOR is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels. 1.6 Primary Prevention of Cardiovascular Disease In individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age ≥ 50 years old in men and ≥ 60 years old in women, hsCRP ≥ 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, CRESTOR is indicated to: ••reduce the risk of stroke ••reduce the risk of myocardial infarction ••reduce the risk of arterial revascularization procedures 1.7 Limitations of Use CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. Launch Date 2003
Atherosclerosis 74 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021366s016lbl.pdf	Primary	Approved 8429	CRESTOR Approved Use CRESTOR is an HMG Co-A reductase inhibitor indicated for: ••patients with primary hyperlipidemia and mixed dyslipidemia as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C (1.1) ••patients with hypertriglyceridemia as an adjunct to diet (1.2) ••patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet (1.3) ••patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB (1.4) ••slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to diet (1.5) ••pediatric patients 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy (1.1) ••risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors (1.6) Limitations of use (1.7): ••CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. 1.1 Hyperlipidemia and Mixed Dyslipidemia CRESTOR is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, nonHDL-C, and triglycerides and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and nonpharmacological interventions alone has been inadequate. Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH) Adjunct to diet to reduce Total-C, LDL-C and ApoB levels in adolescent boys and girls, who are at least one year post-menarche, 10-17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C > 190 mg/dL or > 160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors. 1.2 Hypertriglyceridemia CRESTOR is indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. 1.3 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) CRESTOR is indicated as an adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia). 1.4 Homozygous Familial Hypercholesterolemia CRESTOR is indicated as adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL-C, Total-C, and ApoB in adult patients with homozygous familial hypercholesterolemia. 1.5 Slowing of the Progression of Atherosclerosis CRESTOR is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels. 1.6 Primary Prevention of Cardiovascular Disease In individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age ≥ 50 years old in men and ≥ 60 years old in women, hsCRP ≥ 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, CRESTOR is indicated to: ••reduce the risk of stroke ••reduce the risk of myocardial infarction ••reduce the risk of arterial revascularization procedures 1.7 Limitations of Use CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. Launch Date 2003

C_max

Value	Dose	Analyte	Population
25.86 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
44.99 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10.22 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
216.77 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
311.35 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
75.93 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
13.33 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
15.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13.01 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18042475	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ROSUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
12% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208647s000lbl.pdf			ROSUVASTATIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	Disc. AE: Cardiovascular disorder, Myocardial infarction... AEs leading to discontinuation/dose reduction: Cardiovascular disorder (grade 5, 0.3%) Myocardial infarction (1.6%) Stroke (0.4%) Cardiovascular disorder (7.5%) Aspartate aminotransferase increased (0.4%) Alanine aminotransferase increased (0.7%) Creatine kinase increased (grade 3, 0.3%) Creatine kinase increased (grade 4, 0.1%) Proteinuria (3.8%) Creatinine increased (3.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
2 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Co-administed with:: erlotinib, p.o(150 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/27036206 Page: p.4, 8	unhealthy, 58 n = 8 Health Status: unhealthy Condition: Cancer Age Group: 58 Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/27036206 Page: p.4, 8	DLT: Rhabdomyolysis... Dose limiting toxicities: Rhabdomyolysis (grade 5, 12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/27036206 Page: p.4, 8
1 mg/kg 1 times / day multiple, oral MTD Dose: 1 mg/kg, 1 times / day Route: oral Route: multiple Dose: 1 mg/kg, 1 times / day Co-administed with:: erlotinib, p.o(150 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/27036206 Page: p.4, 8	unhealthy, 58 n = 10 Health Status: unhealthy Condition: Cancer Age Group: 58 Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/27036206 Page: p.4, 8	Sources: https://pubmed.ncbi.nlm.nih.gov/27036206 Page: p.4, 8

AEs

AE	Significance	Dose	Population
Aspartate aminotransferase increased	0.4% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Stroke	0.4% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Alanine aminotransferase increased	0.7% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Myocardial infarction	1.6% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Creatinine increased	3.3% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Proteinuria	3.8% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Cardiovascular disorder	7.5% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Creatine kinase increased	grade 3, 0.3% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Creatine kinase increased	grade 4, 0.1% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Cardiovascular disorder	grade 5, 0.3% Disc. AE	40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085	unhealthy, 57.4±8.6 n = 691 Health Status: unhealthy Condition: Coronary atherosclerosis Age Group: 57.4±8.6 Sex: M+F Population Size: 691 Sources: https://pubmed.ncbi.nlm.nih.gov/22085316 Page: p.2085
Rhabdomyolysis	grade 5, 12.5% DLT, Disc. AE	2 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Co-administed with:: erlotinib, p.o(150 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/27036206 Page: p.4, 8	unhealthy, 58 n = 8 Health Status: unhealthy Condition: Cancer Age Group: 58 Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/27036206 Page: p.4, 8

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 450 18 P-gp 1461 BCRP 699	CYP2C19 991 OATP1B1 406 OATP1B3 350 OATP2B1 104 BCRP 561 NTCP 17 OAT3 339	CYP 450 10

Drug as perpetrator

Target	Modality	Activity
CYP 450 20	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_Pharmr_P2.pdf#page=16 Page: 16.0	no
CYP 450 20	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_Pharmr_P2.pdf#page=16 Page: 16.0	no
P-gp 1650	inhibitor 3277 Sources: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.25295 Page: 11.0	no
BCRP 773	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/rosuvastatin/	yes [Ki 15.4 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_BioPharmr.pdf#page=51 Page: 51.0	major	no (co-administration study) Comment: fluconazole (inhibitor) had no statistically significant interaction with drug Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_BioPharmr.pdf#page=51 Page: 51.0
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_BioPharmr.pdf#page=51 Page: 51.0	minor
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_BioPharmr.pdf#page=51 Page: 51.0	minor	no (co-administration study) Comment: fluconazole (inhibitor) had no statistically significant interaction with drug Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_BioPharmr.pdf#page=51 Page: 51.0
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_BioPharmr.pdf#page=51 Page: 51.0	minor	yes (co-administration study) Comment: Itraconazole increased exposure of rosuvastatin based on AUC by 39% and 28%; no significant effect of ketoconazole on rosuvastatin; Rosuvastatin exposure decreased in presence of erythromycin for 20% and 31% of AUC and Cmax, respectively; Cyclosporine increased rosuvastatin Cmax and AUC by ~10- and 7-fold, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_BioPharmr.pdf#page=51 Page: 51.0
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18236139/	yes
NTCP 17	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16697742/	yes
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17585018/	yes
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18617601/	yes
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18617601/	yes
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18617601/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/22081364/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:38545	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:38545
MolPort	MolPort-000-883-884	https://www.molport.com/shop/molecule-link/MolPort-000-883-884
ZINC	ZINC000001535101	http://zinc15.docking.org/substances/ZINC000001535101
eMolecules	877496	https://www.emolecules.com/cgi-bin/more?vid=877496

PubMed

Title	Date	PubMed
A new HMG-CoA reductase inhibitor, rosuvastatin, exerts anti-inflammatory effects on the microvascular endothelium: the role of mevalonic acid.	2001 Jun	11375257
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.	2001 Mar 8	11256847
Structural mechanism for statin inhibition of HMG-CoA reductase.	2001 May 11	11349148
Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels.	2003 Jun 1	12767421
The statin wars.	2003 Nov 1	14602449
Effects of switching statins on lipid and apolipoprotein ratios in the MERCURY I study.	2005 Apr 20	15823640
Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin.	2005 Aug	15901796
Aggravation of focal cerebral ischemia by tissue plasminogen activator is reversed by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor but does not depend on endothelial NO synthase.	2005 Feb	15625301
Comparison of rosuvastatin with atorvastatin, simvastatin and pravastatin in achieving cholesterol goals and improving plasma lipids in hypercholesterolaemic patients with or without the metabolic syndrome in the MERCURY I trial.	2005 Jul	15955130
Chronic treatment with rosuvastatin modulates nitric oxide synthase expression and reduces ischemia-reperfusion injury in rat hearts.	2005 Jun 1	15914111
Rosuvastatin, but not simvastatin, provides end-organ protection in stroke-prone rats by antiinflammatory effects.	2005 Mar	15681303
Rosuvastatin-associated hepatitis with autoimmune features.	2005 May	15827453
Binding thermodynamics of statins to HMG-CoA reductase.	2005 Sep 6	16128575
Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.	2006 Apr 5	16533939
Rosuvastatin 5 and 10 mg/d: a pilot study of the effects in hypercholesterolemic adults unable to tolerate other statins and reach LDL cholesterol goals with nonstatin lipid-lowering therapies.	2006 Jun	16860175
Rosuvastatin treatment protects against nitrate-induced oxidative stress in eNOS knockout mice: implication of the NAD(P)H oxidase pathway.	2006 Jun	16633368
Statin-associated myasthenia gravis: report of 4 cases and review of the literature.	2006 Mar	16609346
Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors.	2007 Aug 15	17574412
Statin treatment and 3' polyadenylation of eNOS mRNA.	2007 Dec	17916773
Myopathy caused by a combination rosuvastatin and fenofibrate.	2007 Feb	17571748
McArdle disease with rhabdomyolysis induced by rosuvastatin: case report.	2007 Sep	17952291
Statin therapy alters the relationship between apolipoprotein B and low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol targets in high-risk patients: the MERCURY II (Measuring Effective Reductions in Cholesterol Using Rosuvastatin) trial.	2008 Aug 19	18702965
In-vivo effects of simvastatin and rosuvastatin on global gene expression in peripheral blood leucocytes in a human inflammation model.	2008 Feb	18192897
Rationale and design of the carotid plaque in human for all evaluations with aggressive rosuvastatin therapy (CHALLENGER trial): evaluation by magnetic resonance imaging.	2009 Jan	19057091
Rosuvastatin prevents endothelial cell death and reduces atherosclerotic lesion formation in ApoE-deficient mice.	2009 Jan	18162361
WT-1 mRNA expression is modulated by nitric oxide availability and Hsp70 interaction after neonatal unilateral ureteral obstruction.	2010 Dec	21443142
Functional characterization of mouse organic anion transporting peptide 1a4 in the uptake and efflux of drugs across the blood-brain barrier.	2010 Jan	19833843
Biliary efflux transporters involved in the clearance of rosuvastatin in sandwich culture of primary rat hepatocytes.	2010 Mar	19853032
Rosuvastatin attenuates the elevation in blood pressure induced by overexpression of human C-reactive protein.	2011 Jul	21562509
Rosuvastatin induces apoptosis in cultured human papillary thyroid cancer cells.	2011 Jul	21478229
Rosuvastatin prevents myocardial necrosis in an experimental model of acute myocardial infarction.	2011 May	21445530
Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter.	2013 Jul	23564645
Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin in sandwich-cultured rat hepatocytes.	2014 Sep	24909372

Patents

Sample Use Guides

In Vivo Use Guide

The dose range for CRESTOR (rosuvastatin calcium) is 5 to 40 mg orally once daily. The usual starting dose is 10-20 mg.

Route of Administration: Oral

In Vitro Use Guide

HUVECs treated with 30 mM glucose were used to simulate high-glucose conditions, and rosuvastatin concentrations ranging from 0.1 to 10 nM were used.

Name

Type

Language

ROSUVASTATIN

Official Name

English

ROSUVASTATIN [HSDB]

Common Name

English

ZD4522

Code

English

ROSUVASTATIN [MI]

Common Name

English

6-HEPTENOIC ACID, 7-(4-(4-FLUOROPHENYL)-6-(1-METHYLETHYL)-2-(METHYL(METHYLSULFONYL)AMINO)-5-PYRIMIDINYL)-3,5-DIHYDROXY-, (3R,5S,6E)-

Common Name

English

(3R,5S,6E)-7-(4-(4-FLUOROPHENYL)-6-ISOPROPYL-2-(METHYL(METHYLSULFONYL)AMINO)PYRIMIDIN-5-YL)-3,5-DIHYDROXYHEPT-6-ENOIC ACID

Systematic Name

English

ROSUVASTATIN [VANDF]

Common Name

English

Rosuvastatin [WHO-DD]

Common Name

English

CRESTON

Brand Name

English

rosuvastatin [INN]

Common Name

English

X-PLENDED

Common Name

English

ZD-4522

Code

English

Classification Tree Code System Code

WHO-ATC

C10BX09