PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
ribavirin

2D structure

Overview

Generic Names: RBV; Ribavirin Triphosphate; Ribavirina [INN-Spanish]; Ribavirine [INN-French]; Ribavirinum [INN-Latin]
Trade Names: Copegus; RIBAV; RTC; RTCA; RTP; Rebetol; Rebetron; Rebretron; Ribamide; Ribamidil; Ribamidyl; Ribasphere; Ribavirin Capsules; Ribavirin-TP; Tribavirin; Varazid; Vilona; Viramid; Virazid; Virazole; Virazole 5'-triphosphate
Brand Mixtures: Rebetron (Schering-Plough) (Ribavirin + Interferon alpha)
PharmGKB Accession Id: PA451241

Description

A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. PubChem (source: Drug Bank)

Indication

For the treatment of chronic hepatitis C and for respiratory syncytial virus (RSV). (source: Drug Bank)

ATC Therapeutic Category

  • J05AB:Nucleosides and nucleotides excl. reverse transcriptase inhibitors

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Ribavirin is readily phosphorylated intracellularly by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. Ribavirin triphosphate (RTP) is a potent competitive inhibitor of inosine monophosphate (IMP) dehydrogenase, viral RNA polymerase and messenger RNA (mRNA) guanylyltransferase (viral). Guanylyltranserase inhibition stops the capping of mRNA. These diverse effects result in a marked reduction of intracellular guanosine triphosphate (GTP) pools and inhibition of viral RNA and protein synthesis. Ribavirin is also incorporated into the viral genome causing lethal mutagenesis and a subsequent decrease in specific viral infectivity. (source: Drug Bank)

Pharmacology

Ribavirin is an anti-viral drug active against a number of DNA and RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material. The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to it's resemblence to building blocks of the RNA molecules. The oral form is used in the treatment of hepatitis C, in combination with interferon drugs. The aerosol form is used to treat respiratory syncytial virus-related diseases in children. The primary serious adverse effect of ribavirin is hemolytic anemia, which may worsen preexisting cardiac disease. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Results of <i>in vitro</i> studies using both human and rat liver microsome preparations indicated little or no cytochrome P450 enzyme-mediated metabolism of ribavirin, with minimal potential for P450 enzyme-based drug interactions. Ribavirin has two pathways of metabolism: (1) a reversible phosphorylation pathway in nucleated cells; and (2) a degradative pathway involving deribosylation and amide hydrolysis to yield a triazole carboxylic acid metabolite. (source: Drug Bank)

Absorption

Rapidly and extensively absorbed following oral administration. However, due to first-pass metabolism, the absolute bioavailability averages 64%. (source: Drug Bank)

Toxicity

Side effects include "flu-like" symptoms, such as headache, fatigue, myalgia, and fever. The LD<sub>50</sub> in mice is 2 g/kg orally and is associated with hypoactivity and gastrointestinal symptoms (estimated human equivalent dose of 0.17 g/kg, based on body surface area conversion). (source: Drug Bank)

Isomeric SMILES Code:

C1=NC(=NN1[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O)C(=O)N (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs12980275 at chr19:44423623 in IL28B
    Risk or phenotype-associated allele: G. Phenotype: This variant is associated with null virological response (NVR) and sustained virologic response (SVR) in Janapese patients with hepatitis C virus infection treated with PEG-INF-alpha plus ribavirin. Study size: Initial sample:154; Replication Sample: 172. Study population/ethnicity: Japanese. Significance metric(s): P=1.6x10-13 (NVR); P = 3.99 x 10(-24)(SVR). Type of association: GN; CO
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis C, Hepatitis C, Chronic
    Evidence:
    PMID:19749757
  2. rs8105790 at chr19:44424341 in IL28B
    Phenotype: This variant is associated with null virological response (NVR) in Janapese patients with hepatitis C virus infection treated with PEG-INF-alpha plus ribavirin. Study size: Initial sample:154; Replication Sample: 172. Study population/ethnicity: Japanese. Significance metric(s): P=1.98 x 10(-31) (NVR). Type of association: GN; CO
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis C, Hepatitis C, Chronic
    Evidence:
    PMID:19749757
  3. rs11881222 at chr19:44426763 in IL28B
    Phenotype: This variant is associated with null virological response (NVR) in Janapese patients with hepatitis C virus infection treated with PEG-INF-alpha plus ribavirin. Study size: Initial sample:154; Replication Sample: 172. Study population/ethnicity: Japanese. Significance metric(s): P=2.84 x 10(-31) (NVR). Type of association: GN; CO
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis C, Hepatitis C, Chronic
    Evidence:
    PMID:19749757
  4. rs8103142 at chr19:44426946 in IL28B
    Phenotype: This variant is associated with null virological response (NVR) in Janapese patients with hepatitis C virus infection treated with PEG-INF-alpha plus ribavirin. Study size: 304. Study population/ethnicity: Japanese. Significance metric(s): P=1.4 x 10(-29) (NVR). Type of association: GN; CO
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis C, Hepatitis C, Chronic
    Evidence:
    PMID:19749757
  5. rs8103142 at chr19:44426946 in IL28B
    Phenotype: Sequencing of the IL28B gene in 96 individuals found this SNP to be highly associated with rs12979860 (r-squared > 0.85), which, in a GWAS done in patients of European ancestry, African-Americans and Hispanics was significantly associated with rate of SVR (sustained virological response) to treatment of chronic Hepatitis C genotype I infection with peginterferon-alpha-2a or -2b combined with ribavirin.
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis, Hepatitis C, Liver Cirrhosis
    Evidence:
    PMID:19684573
  6. rs28416813 at chr19:44427484 in IL28B
    Phenotype: This variant is associated with null virological response (NVR) in Janapese patients with hepatitis C virus infection treated with PEG-INF-alpha plus ribavirin. Study size: 304. Study population/ethnicity: Japanese. Significance metric(s): P=5.5 x 10(-28) (NVR). Type of association: GN; CO
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis C, Hepatitis C, Chronic
    Evidence:
    PMID:19749757
  7. rs28416813 at chr19:44427484 in IL28B
    Phenotype: Sequencing of the IL28B gene in 96 individuals found this SNP to be highly associated with rs12979860 (r - squared > 0.85), which, in a GWAS done in patients of European ancestry, African-Americans and Hispanics was significantly associated with rate of SVR (sustained virological response) to treatment of chronic Hepatitis C genotype I infection with peginterferon-alpha-2a or -2b combined with ribavirin.
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis, Hepatitis C, Liver Cirrhosis
    Evidence:
    PMID:19684573
  8. rs4803219 at chr19:44427759 in IL28B
    Phenotype: This variant is associated with null virological response (NVR) in Janapese patients with hepatitis C virus infection treated with PEG-INF-alpha plus ribavirin. Study size: 304. Study population/ethnicity: Japanese. Significance metric(s): P=2.4 x 10(-29) (NVR). Type of association: GN; CO
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis C, Hepatitis C, Chronic
    Evidence:
    PMID:19749757
  9. rs12979860 at chr19:44430627 in IL28B
    Phenotype/ associated allele: A GWAS showed that, in patients of European ancestry, the CC genotype of this SNP is associated with a twofold (95% CI 1.8-2.3) greater rate of SVR (sustained virological response) than is the TT genotype to treatment of chronic Hepatitis C genotype I infection with peginterferon-alpha-2a or -2b combined with ribavirin. In African -Americans, the response rate ratio is in the same direction, but three-fold (95% CI 1.9-4.7) . In Hispanics, the response ratio is two-fold (95% CI 1.4-3.2). The overall genome-wide association has significance p = 1.37 x 10 -28. Based upon the allele frequency in different population groups, this polymorphism appears to explain about half of the response rate difference between different populations. An association between baseline viral load and genotype was also found. Study size: 1671 total, including European-Americans: 871; African-Americans: 191; Hispanics: 75. Type of association: GN;PD;CO.
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis, Hepatitis C, Liver Cirrhosis
    Evidence:
    PMID:19684573
  10. rs8099917 at chr19:44435005 in IL28B
    Risk or phenotype-associated allele: G. Phenotype: This variant is associated with null virological response (NVR) and sustained virologic response (SVR) in Janapese patients with hepatitis C virus infection treated with PEG-INF-alpha plus ribavirin. Study size: Initial sample:154; Replication Sample: 172. Study population/ethnicity: Japanese. Significance metric(s): P=3.11 x 10(-15) (NVR); P = 1.11 x 10(-27)(SVR). Type of association: GN; CO
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis C, Hepatitis C, Chronic
    Evidence:
    PMID:19749757
  11. rs7248668 at chr19:44435661 in IL28B
    Phenotype: This variant is associated with null virological response (NVR) in Janapese patients with hepatitis C virus infection treated with PEG-INF-alpha plus ribavirin. Study size: Initial sample:154; Replication Sample: 172. Study population/ethnicity: Japanese. Significance metric(s): P=1.8 x 10(-30) (NVR). Type of association: GN; CO
    Related Drugs:
    interferon alfa-2a, recombinant, ribavirin
    Related Diseases:
    Hepatitis C, Hepatitis C, Chronic
    Evidence:
    PMID:19749757
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
IL28B
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
NAT2
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
SLC28A1
  •   
  •   
  •   
  • FA
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
SLC28A2
  •   
  •   
  •   
  • FA
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
SLC29A1
  •   
  •   
  •   
  • FA
  • GN
Publications

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

Drug Targets

Gene Description
NT5C2 Uncurated Annotation (source: Drug Bank)
IMPDH1 Uncurated Annotation (source: Drug Bank)
ENPP1 Uncurated Annotation (source: Drug Bank)

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

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
cancer or viral infections
  •   
  •   
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Hepatitis
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Hepatitis C
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Hepatitis C, Chronic
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants

Non-Curated Information

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

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

  1. SLC28A2 Functional Protein Variants
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • FA
    Submitted by Kathleen M. Giacomini, PhD involving SLC28A2, and ribavirin
  2. SLC29A1 Functional Protein Variants
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • FA
    Submitted by Kathleen M. Giacomini, PhD involving SLC29A1, , 6-o-phosphoryl inosine monophosphate, cytarabine, gemcitabine, ribavirin and uridine

Additional Datasets

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

  1. Physicochemical determinants of human renal clearance
  2. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

Downloads

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LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00811
KEGG Drug ID:
D00423
PubChem Compound ID:
37542
PubChem Substance ID:
178906

Common Searches

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Non-Curated Publications

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

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