General
Preferred name
pravastatin
Synonyms
PRAVASTATIN SODIUM ()
Pravastatin sodium salt ()
CS-514 (sodium) ()
CS-514 Sodium ()
CS-514 (sodium)CS-514 Sodium ()
Mevalotin ()
Pravastatin (sodium) ()
CS-514 ()
Eptastatin Sodium ()
Liplat ()
SQ-31000 ()
NSC-759253 ()
Elisor ()
Dehypotin protect ()
SQ-31,000 ()
Lipemol ()
Lipostat ()
Pravachol ()
Pravastatine ()
Pravastatina ()
C10AA03 ()
Pravator ()
Pravastatin (sodium salt) ()
Pravastatin-d3 (sodium salt) ()
P&D ID
PD010187
CAS
115873-26-2
81093-37-0
81131-70-6
1329836-90-9
Tags
available
drug
probe
Approved by
FDA
First approval
1991
Drug indication
Hypercholesterolaemia
Antihyperlipidemic
Drug Status
approved
Max Phase
4.0
Probe info
Probe selectivity
protein-selective
Probe type
P&D approved
calculated probe
Probe sources
High-quality chemical probes
Probe Miner (suitable probes)
Probe targets
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE The reported elimination half-life of pravastatin is reported to be of 1.8 hours.[A34502]
MOA Pravastatin is a specific inhibitor of the hepatic HMG-CoA reductase in humans.[T274] The inhibition of this enzyme produces a reduction in cholesterol biosynthesis as HMG-CoA reductase activity is an early-limiting step in cholesterol biosynthesis.[A177397]; ; The inhibitory mechanism of action produces a reduction in cholesterol synthesis which in order has been observed to increase the number of LDL receptors on cell surfaces and an enhancement in receptor-mediated metabolism of LDL and clearance.[A177415]; ; On the other hand, pravastatin-driven inhibition of LDL production inhibits hepatic synthesis of VLDL as the LDL is the precursor for these molecules.[A177436]
ROE From the administered dose of pravastatin, about 70% is eliminated in the feces while about 20% is obtained in the urine.[T357]; ; When pravastatin is administered intravenously, approximately 47% of the administered dose is eliminated via the urine with 53% of the dose eliminated either via biotransformation of biliary.[F4603]
METABOLISM After initial administration, pravastatin undergoes extensive first-pass extraction in the liver.[A34502] However, pravastatin's metabolism is not related to the activity of the cytochrome P-450 isoenzymes and its processing is performed in a minor extent in the liver. Therefore, this drug is highly exposed to peripheral tissues.[A177682] ; ; The metabolism of pravastatin is ruled mainly by the presence of glucuronidation reactions with very minimal intervention of CYP3A enzymes. After metabolism, pravastatin does not produce active metabolites.[A34502] This metabolism is mainly done in the stomach followed by a minor portion of renal and hepatic processing.[A39676]; ; The major metabolite formed as part of pravastatin metabolism is the 3-alpha-hydroxy isomer. The activity of this metabolite is very clinically negligible.[F4603]
ABSORPTION Pravastatin is absorbed 60-90 min after oral administration and it presents a low bioavailability of 17%.[A34502] This low bioavailability can be presented due to the polar nature of pravastatin which produces a high range of first-pass metabolism and incomplete absorption.[T239]; ; Pravastatin is rapidly absorbed from the upper part of the small intestine via proton-coupled carrier-mediated transport to be later taken up in the livery by the sodium-independent bile acid transporter.[A39676] The reported time to reach the peak serum concentration in the range of 30-55 mcg/L is of 1-1.5 hours with an AUC ranging from 60-90 mcg.h/L.[A177907]
DESCRIPTION Pravastatin is a statin anti-dyslipidemia drug. Chemically the compound is a derivative of (compactin), which was originally isolated from Penicillium citrinum. (GtoPdb)
PHARMACODYNAMICS The action of pravastatin on the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase produces an increase in the expression of hepatic LDL receptors which in order decreases the plasma levels of LDL cholesterol.[T274]; ; The effect of pravastatin has been shown to significantly reduce the circulating total cholesterol, LDL cholesterol, and apolipoprotein B. As well, it modestly reduces very low-density-lipoproteins (VLDL) cholesterol and triglycerides while increasing the level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A.[F4603]; ; In clinical trials with patients with a history of myocardial infarction or angina with high total cholesterol, pravastatin decreased the level of total cholesterol by 18%, decreased of LDL by 27%, decreased of triglycerides by 6% and increased of high-density lipoprotein (HDL) by 4%. As well, there was reported a decrease in risk of death due to coronary disease of 24%.[A177682] ; ; When coadministered with [cholestyramine], pravastatin can reduce by 50% the levels of LDL and slow the progression of atherosclerosis and the risk of myocardial infarction and death.[T274]
INDICATION Pravastatin is indicated for primary prevention of coronary events hypercholesterolemic patients without clinical evidence of coronary heart disease. Its use includes the reduction of risk on myocardial infarction, undergoing myocardial revascularization procedures and cardiovascular mortality.[T274]; ; As well, pravastatin can be used as a secondary prevention agent for cardiovascular events in patients with clinically evident coronary heart disease. This indication includes the reduction of risk of total mortality by reducing coronary death, myocardial infarction, undergoing myocardial revascularization procedures, stroke, and stroke/transient ischemic attack as well as to slow the progression of coronary atherosclerosis.[T274]; ; The term cardiovascular events correspond to all the incidents that can produce damage to the heart muscle including the interruption of blood flow.[L6028]; ; As adjunctive therapy to diet, pravastatin is used in:; ; - Patients with primary hypercholesterolemia and mixed dyslipidemias including hyperlipidemia type IIa and IIb.; - Patients with elevated serum triglycerides including type IV hyperlipidemia.; - Patients with heterozygous familial hypercholesterolemia in patients over 8 years of age with low-density lipoprotein (LDL) cholesterol higher than 190 mg/dl after diet modifications or LDL levels higher than 160 mg/dl and familial history of premature cardiovascular diseases or at least two cardiovascular risk factors.[T274]; ; In patients that do not respond adequately to diet, pravastatin is used to treat patients with primary dysbetalipoproteinemia (type III hyperlipidemia).[T274] ; ; Dyslipidemia is defined as an elevation of plasma cholesterol, triglycerides or both as well as to the presence of low levels of high-density lipoprotein. This condition represents an increased risk for the development of atherosclerosis.[L6025]
TOXICITY The reported oral LD50 of pravastatin in mice is of 8939 mg/kg.[MSDS] There haven't been significant overdosage reports however, in the case of overdosage, symptomatic treatment is recommended along with laboratory monitoring and supportive measures.[FDA label]; ; In carcinogenic studies, high dose administration of pravastatin has been reported to increase the incidence of hepatocellular carcinomas in males and lung carcinomas in females. There is no evidence relating the administration of pravastatin with mutagenicity in different assays not to produce effects in fertility or reproductive potential.[FDA label]
DESCRIPTION RIP1 kinase inhibitor; inhibits necroptosis (Tocris Bioactive Compound Library)
DESCRIPTION HMG-CoA reductase inhibitor (Tocriscreen Plus)
DESCRIPTION HMG-CoA reductase inhibitor (Tocriscreen Total)
DESCRIPTION Pravastatin is an antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase with IC50 of 5.6 μM. It is used in combination with diet, exercise, and weight loss for lowering cholesterol and preventing cardiovascular disease. It is a synthetic lipid-lowering agent. It lowers plasma cholesterol and lipoprotein levels, and modulates immune responses by suppressing major histocompatibility complex II on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. It is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease. It is used to reduce LDL cholesterol and triglyceride levels and increase HDL cholesterol in the prevention of cardiovascular disease. (BOC Sciences Bioactive Compounds)
Cell lines
3
Organisms
3
Compound Sets
34
AdooQ Bioactive Compound Library
A11912
BOC Sciences Bioactive Compounds
pravastatin-cas-81093-37-0-item-77797
Cayman Chemical Bioactives
10010343
25464
ChEMBL Approved Drugs
CHEMBL690
CHEMBL1144
ChEMBL Drugs
CHEMBL690
CHEMBL1144
Concise Guide to Pharmacology 2017/18
2953
Concise Guide to Pharmacology 2019/20
2953
Concise Guide to Pharmacology 2021/22
2953
Concise Guide to Pharmacology 2023/24
2953
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB00175
DrugBank Approved Drugs
DB00175
DrugCentral
2239
DrugCentral Approved Drugs
2239
DrugMAP
DM6A0X7
DrugMAP Approved Drugs
DM6A0X7
EU-OPENSCREEN Bioactive Compound Library
EOS101660
Guide to Pharmacology
2953
High-quality chemical probes
PD010187
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL690
CHEMBL1144
MedChem Express Bioactive Compound Library
HY-B0165A
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
KXO2KT9N0G
NIH Clinical Collections (NCC)
NPC Screening Collection
Prestwick Chemical Library
Probe Miner (suitable probes)
P04035/246932
ReFrame library
Selleckchem Bioactive Compound Library
pravastatin-pravachol
pravastatin
TargetMol Bioactive Compound Library
T0672
Tocris Bioactive Compound Library
2318
Tocriscreen Plus
2318
Tocriscreen Total
External IDs
80
Properties
(calculated by RDKit )
Molecular Weight
424.25
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
4
Rotatable Bonds
10
Ring Count
2
Aromatic Ring Count
0
cLogP
2.44
TPSA
124.29
Fraction CSP3
0.74
Chiral centers
8.0
Largest ring
6.0
QED
0.4
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Enzymes
Target
Autophagy
HMG-CoA Reductase (HMGCR)
HMG-CoA Reductase
HMGCR, SLCO1B1
Ferroptosis
Pathway
Metabolic Enzyme/Protease
Metabolism
Apoptosis
MOA
Inhibitor
HMGCR inhibitor
Disease Area
endocrinology, cardiology
Indication
hypercholesterolemia, myocardial infarction, hyperlipidemia
Biosynthetic Origin
Polyketide
Therapeutic Indication
Hypocholesterolemic
Therapeutic Class
Cardiovascular
Anticholesteremic Agents
Solubility
10 mM in H2O (free soluble)
Source data