Drug/Small Molecule:

pravastatin

Overview

Generic Names:	Pravastatin Sodium; Pravastatina [Spanish]; Pravastatine [French]; Pravastatinum [Latin]
Trade Names:	Compactin; Elisor; Lipostat; Mevalotin; Mevastatin; Mevinolin; Oliprevin; Pravachol; Pravaselect; Selectin; Selipran; Vasten
PharmGKB Accession Id:	PA451089

Description

Indication

ATC Therapeutic Category

• C10AA:HMG CoA reductase inhibitors

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Pharmacology

Food Interactions

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Protein Binding

Absorption

Toxicity

Isomeric SMILES Code:

In-Depth Annotations ()

1. rs17244841 at chr5:74678611 in HMGCR
   Associated with total cholesterol and LDL-cholesterol levels.

   Variant Name:

   HMGCR:SNP 12

   Related Drugs:

   pravastatin

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforHMGCR-SNP12
   

2. rs17238540 at chr5:74691254 in HMGCR
   Conflicting studies, but this SNP has been associated with total cholesterol and LDL-cholesterol levels.

   Variant Name:

   HMGCR:SNP 29

   Related Drugs:

   pravastatin

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp
   

3. rs4149015 at chr12:21174589 in SLCO1B1
   Associated with increased pravastatin plasma AUC.

   Variant Name:

   SLCO1B1:G-11187A

   Related Drugs:

   pravastatin

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp
   

4. rs2306283 at chr12:21221005 in SLCO1B1
   Associated with decreased pravastatin plasma AUC.

   Variant Name:

   SLCO1B1:N130D

   Related Drugs:

   pravastatin

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforSLCO1B1-N130D
   

5. rs4149056 at chr12:21222816 in SLCO1B1
   Associated with increased pravastatin plasma AUC.

   Variant Name:

   SLCO1B1:V174A

   Related Drugs:

   pravastatin

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp
   

Curated Annotations ()

1. rs5186 at chr3:149942678 in AGTR1
   In the REGRESS study of 885 Dutch male patients with stable coronary artery disease, patients who carried both the ACE:I/D DD genotype and AGTR1:116A>C CC genotype had significantly more ischaemic events during the two year follow up than those carrying other genotype combinations.

   Variant Name:

   AGTR1:116A>C, AT(1)R A1166C

   Related Drugs:

   pravastatin

   Related Diseases:

   Coronary Artery Disease

   Evidence:

   PMID:11250978
   

2. rs12654264 at chr5:74684359 in HMGCR
   Risk or phenotype-associated allele: A. Phenotype: Homozygotes of the A variant taking statins had lower odds of developing colorectal cancer than those with the TT variant, with heterozygotes showing intermediate risk. The A variant was also asssociated with lower serum LDL. Study size: 4187. Study population/ethnicity: Molecular Epidemiology of Colorectal Cancer (MECC) study, Jewish, Arab, Israel. Significance metric(s): p = 0.0012. Type of association: PD; CO.

   Variant Name:

   noncoding SNP located in intron 12 of HMGCR IVS 12

   Related Drugs:

   hmg coa reductase inhibitors, pravastatin, simvastatin

   Related Diseases:

   Colorectal Neoplasms

   Evidence:

   PMID:20403997
   

3. rs20455 at chr6:39433056 in KIF6
   This variant is associated with an increased risk of myocardial infarction and coronary heart diseases.Pravastatin treatment substantially reduced that risk.

   Variant Name:

   KIF6:Trp719Arg

   Related Drugs:

   pravastatin

   Related Diseases:

   Myocardial Infarction

   Evidence:

   PMID:18073581
   PMID:18222353
   PMID:18222354
   PMID:18222355
   

4. rs1935349 at chr10:92584323 in HTR7
   This variant is found to be a risk marker for statin induced myalgia

   Related Drugs:

   atorvastatin, pravastatin, simvastatin

   Related Diseases:

   Myalgia unspecified

   Evidence:

   PMID:17600820
   

5. rs2276307 at chr11:113309097 in HTR3B
   This variant is found to be a risk marker for statin induced myalgia

   Related Drugs:

   atorvastatin, pravastatin, simvastatin

   Related Diseases:

   Myalgia unspecified

   Evidence:

   PMID:17600820
   

6. rs5443 at chr12:6825136 in GNB3, USP5
   This variant is associated with statin response. Patients carring T allele have less risk of MI and are more likely to benefit from statin therapy in a hypercholesterolemic population of antihypertensive drug users.

   Variant Name:

   GNB3:825C>T; GNB3:Ser275Ser

   Related Drugs:

   atorvastatin, fluvastatin, hmg coa reductase inhibitors, lovastatin, pravastatin, rosuvastatin, simvastatin

   Related Diseases:

   Hypercholesterolemia

   Evidence:

   PMID:18551043
   

7. rs4149015 at chr12:21174589 in SLCO1B1
   Subjects with the G variant showed higher plasma pravastatin AUC and Cmax relative to A variant

   Variant Name:

   SLCO1B1:11187G>A

   Related Drugs:

   pravastatin

   Evidence:

   PMID:15226675
   

8. rs2306283 at chr12:21221005 in SLCO1B1
   Variant with G allele showed mixed results: NO change in in vitro transport of estrone sulfate but decreased plasma AUC of pravastatin, endogenous bile acids

   Variant Name:

   SLCO1B1:388A>G. SLCO1B1:*1b

   Related Drugs:

   pravastatin

   Evidence:

   PMID:11477075
   PMID:15116054
   PMID:19387419
   

9. rs4149056 at chr12:21222816 in SLCO1B1
   The cholesterol synthesis rate was higher in CC individuals than in TT individuals. There was no association between this SNP and the short-term effects of statins on cholesterol synthesis rates.

   Variant Name:

   SLCO1B1:c.521T>C, SLCO1B1:p.Val174Ala

   Related Drugs:

   atorvastatin, fluvastatin, hmg coa reductase inhibitors, pravastatin, rosuvastatin, simvastatin

   Evidence:

   PMID:18794729
   

10. rs4149056 at chr12:21222816 in SLCO1B1
    Variant with C allele had reduced transport, relative to variant with T allele (based upon lower plasma AUC) of pravastatin

    Variant Name:

    SLCO1B1:521T>C, SLCO1B1:*5

    Related Drugs:

    pravastatin

    Evidence:

    PMID:12811365
    PMID:17177112
    

11. rs4149056 at chr12:21222816 in SLCO1B1
    Risk or phenotype-associated allele: SLCO1B1*5 allele, defined by rs4149056 (521T>C, Val174Ala). Phenotype: SLCO1B1*5 allele (rs4149056, V174A) was associated with the adverse events from statins (chi-square = 4.2, p = 0.03, FDR = 0.24), with greatest risk with simvastatin. There were significantly more females (66%) with adverse events than females without adverse events (50%) (p < 0.01). Among subjects with adverse effects (n = 99), females bore greater risk of adverse events (OR = 2.0, p = 0.004). In multivariate analysis adjusted for race, female sex (OR = 2.2, p = 0.001) and SLCO1B1*5 genotype (OR = 1.7, p = 0.03) were independently associated with adverse events to statins (p < 0.05 for both). Simvastatin plasma concentration was positively correlated with SLCO1B1*5 both at 20 mg (p = 0.006) and 80 mg (p = 0.03). Study size: 452. Study population/ethnicity: Hypercholesterolemia outpatients given 1 of 3 statins (atorvastatin, simvastatin, or pravastatin) between 2001 and 2002 Significance metric(s): OR (1.7 - 2.2), p < 0.05 Type of association: CO; GN; PK; ADR

    Variant Name:

    SLCO1B1*5, c.521T>C. mRNA 616T>G, p.Val174Ala

    Related Drugs:

    atorvastatin, pravastatin, simvastatin

    Related Diseases:

    Hypercholesterolemia, Muscular Diseases, Myalgia unspecified

    Evidence:

    PMID:19833260
    

12. rs5918 at chr17:42715729 in ITGB3
    Risk or phenotype-associated allele: C. Phenotype: Patients with the PI(A1A2) genotype (C allele carriers) had a higher risk of secondary coronary events which was reduced by pravastatin. There was also an interaction between PI(A1A2) and the ACE:I/D variant and pravastatin response. Study size: 767. Study population/ethnicity: Subset of Cholesterol And Recurrent Events (CARE) trial, men and women with myocardial infarction receiving placebo or pravastatin. Significance metric(s): . Type of association: CO.

    Variant Name:

    ITGB3:1565T>C, ITGB3:Leu33Pro, PI(A2)

    Related Drugs:

    pravastatin

    Related Diseases:

    Myocardial Infarction

    Evidence:

    PMID:11545752
    

The following genes are in curated knowledge about this drug.

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene		Description
HMGCR		(source: Drug Bank)
ABCC2		(source: Drug Bank)
PGGT1B		(source: Drug Bank)
RAC1		(source: Drug Bank)
SLCO1B1		(source: Drug Bank)

PharmGKB Curated Pathways

• Statin Pathway (Cholesterol and Lipoprotein Transport PD)
• Statin Pathway (PK)
• Statin Pathway (Pravastatin PK)

The following drugs are in curated knowledge about this drug.

	Drug	Relationship	Evidence
	ezetimibe	FA	Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug		Description
bezafibrate		Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
colchicine		Increased risk of rhabdomyolysis with this combination (source: Drug Bank)
cyclosporine		Possible myopathy and rhabdomyolysis (source: Drug Bank)
fenofibrate		Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
gemfibrozil		Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. Effects of Pravastatin on Mouse Liver
2. Genetic Variants in Statin associated Adverse Events
3. Pharmacogenetic study of statin therapy and cholesterol reduction
4. Physicochemical determinants of human renal clearance

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.