PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
indinavir

2D structure

Overview

Generic Names: Compound J; Indinavir sulfate
Trade Names: Crixivan
PharmGKB Accession Id: PA449977

Description

A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. PubChem (source: Drug Bank)

Indication

For the treatment of HIV infection. (source: Drug Bank)

ATC Therapeutic Category

  • J05AE:Protease inhibitors

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Indinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles. (source: Drug Bank)

Pharmacology

Indinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Indinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. (source: Drug Bank)

Food Interactions

Avoid excessive or chronic alcohol use.
Avoid taking with grapefruit juice
Take on empty stomach: 1 hour before or 2 hours after meals.
Take with a full glass of water. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Seven metabolites have been identified, one glucuronide conjugate and six oxidative metabolites. In vitro studies indicate that cytochrome P-450 3A4 (CYP3A4) is the major enzyme responsible for formation of the oxidative metabolites. (source: Drug Bank)

Protein Binding

60% (source: Drug Bank)

Absorption

Rapidly absorbed (source: Drug Bank)

Toxicity

Symptoms of overdose include myocardial infarction and angina pectoris. (source: Drug Bank)

Isomeric SMILES Code:

CC(C)(C)NC(=O)[C@@H]1CN(CCN1C[C@H](C[C@@H](Cc2ccccc2)C(=O)N[C@H]3c4ccccc4C[C@H]3O)O)Cc5cccnc5 (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs2740574 at chr7:99220032 in CYP3A, CYP3A4
    A study of 40 protease inhibitor-naive HIV patients found that the CYP3A4*1B polymorphism influenced the pharmacokinetics of indinavir and, to some extent, the biochemical safety of indinavir.
    Variant Name:
    CYP3A4*1B
    Related Drugs:
    indinavir
    Related Diseases:
    HIV Infections
    Evidence:
    PMID:19440701
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
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ABCC2
  •   
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ORM1
  •   
  •   
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ORM2
  •   
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
UGT1A1
  •   
  •   
  • PK
  • FA
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
UGT1A7
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
UGT1A9
  •   
  •   
  • PK
  • FA
  •   
Publications

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

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

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

Drug Interactions

Drug Description
acenocoumarol Uncurated Annotation The protease inhibitor increases the anticoagulant effect (source: Drug Bank)
alprazolam Uncurated Annotation The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
amiodarone Uncurated Annotation Indinavir increases the effect and toxicity of amiodarone (source: Drug Bank)
astemizole Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
atazanavir Uncurated Annotation Increased risk of hyperbilirubinemia with this association (source: Drug Bank)
atorvastatin Uncurated Annotation Increases the effect and toxicity of atorvastatin (source: Drug Bank)
calcium Uncurated Annotation The antacid decreases the absorption of indinavir (source: Drug Bank)
carbamazepine Uncurated Annotation Indinavir increases the effect and toxicity of carbamazepine (source: Drug Bank)
chlordiazepoxide Uncurated Annotation The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
cisapride Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clarithromycin Uncurated Annotation Clarithromycin increases the effect and toxicity of indinavir (source: Drug Bank)
clonazepam Uncurated Annotation The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
cyclosporine Uncurated Annotation The protease inhibitor increases the effect of cyclosporine (source: Drug Bank)
delavirdine Uncurated Annotation Delavirdine increases the effect of indinavir (source: Drug Bank)
diazepam Uncurated Annotation The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
dicumarol Uncurated Annotation The protease inhibitor increases the anticoagulant effect (source: Drug Bank)
efavirenz Uncurated Annotation Efavirenz decreases the effect of indinavir (source: Drug Bank)
erlotinib Uncurated Annotation This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank)
esomeprazole Uncurated Annotation Omeprazole decreases the absorption of indinavir (source: Drug Bank)
estazolam Uncurated Annotation The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
fentanyl Uncurated Annotation The protease inhibitor increases the effect and toxicity of fentanyl (source: Drug Bank)
flurazepam Uncurated Annotation The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
ketoconazole Uncurated Annotation Ketoconazole increases the efefct of indinavir (source: Drug Bank)
lansoprazole Uncurated Annotation Omeprazole decreases the absorption of indinavir (source: Drug Bank)
magnesium Uncurated Annotation The antacid decreases the absorption of indinavir (source: Drug Bank)
magnesium oxide Uncurated Annotation The antacid decreases the absorption of indinavir (source: Drug Bank)
midazolam Uncurated Annotation The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
omeprazole Uncurated Annotation Omeprazole decreases the absorption of indinavir (source: Drug Bank)
pantoprazole Uncurated Annotation Omeprazole decreases the absorption of indinavir (source: Drug Bank)
pimozide Uncurated Annotation The protease inhibitor increases the effect and toxicity of pimozide (source: Drug Bank)
rabeprazole Uncurated Annotation Omeprazole decreases the absorption of indinavir (source: Drug Bank)
rifabutin Uncurated Annotation Rifabutin decreases the effect of indinavir (source: Drug Bank)
rifampin Uncurated Annotation Rifampin decreases the effect of indinavir (source: Drug Bank)
risperidone Uncurated Annotation Increased risk of extrapyramidal symptoms (source: Drug Bank)
saquinavir Uncurated Annotation Possible antagonism of action (source: Drug Bank)
sildenafil Uncurated Annotation The protease inhibitor increases the effect and toxicity of sildenafil (source: Drug Bank)
sunitinib Uncurated Annotation Possible increase in sunitinib levels (source: Drug Bank)
tacrolimus Uncurated Annotation Increases the effect and toxicity of tacrolimus (source: Drug Bank)
terfenadine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
trazodone Uncurated Annotation This strong CYP3A4 inhibitor increases the effect and toxicity of trazodone (source: Drug Bank)
triazolam Uncurated Annotation The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
vardenafil Uncurated Annotation The protease inhibitor increases the effect and toxicity of vardenafil (source: Drug Bank)
vitamin c Uncurated Annotation Vitamin C decreases indinavir levels (source: Drug Bank)
warfarin Uncurated Annotation The protease inhibitor increases the anticoagulant effect (source: Drug Bank)

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
HIV
  •   
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
HIV Infections
  •   
  •   
  • PK
  •   
  • GN
Publications, Variants

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. Genetic Variants in Protease Inhibitor associated Adverse Events
  2. Physicochemical determinants of human renal clearance

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00224
ChEBI ID:
5898
KEGG Compound ID:
C07051
PubChem Compound ID:
5362440
PubChem Substance ID:
197165

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

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

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
Add New Alternate Name
Add New ATC Term
Add Cross Reference
Add a metabolite
Add a text annotation
Add a drug target
hint: enter a gene
    Add a drug interaction
    hint: enter a drug
    PharmGKB® is a registered trademark of HHS and is financially supported by NIH/NIGMS. It is managed at Stanford University (GM61374).
    ©2001-2010 PharmGKB.