U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C36H47N5O4
Molecular Weight 613.7895
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of INDINAVIR ANHYDROUS

SMILES

CC(C)(C)NC(=O)[C@@H]1CN(CC2=CN=CC=C2)CCN1C[C@@H](O)C[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H]4[C@H](O)CC5=C4C=CC=C5

InChI

InChIKey=CBVCZFGXHXORBI-PXQQMZJSSA-N
InChI=1S/C36H47N5O4/c1-36(2,3)39-35(45)31-24-40(22-26-12-9-15-37-21-26)16-17-41(31)23-29(42)19-28(18-25-10-5-4-6-11-25)34(44)38-33-30-14-8-7-13-27(30)20-32(33)43/h4-15,21,28-29,31-33,42-43H,16-20,22-24H2,1-3H3,(H,38,44)(H,39,45)/t28-,29+,31+,32-,33+/m1/s1

HIDE SMILES / InChI

Molecular Formula C36H47N5O4
Molecular Weight 613.7895
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/dosage/indinavir.html

Indinavir is an antiretroviral drug for the treatment of HIV infection. 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.

CNS Activity

Curator's Comment: Median concentration of Indinavir in CSF was 210 nmol/l, which is the threshold for IC95 in vitro. Indinavir is essentially the only PI that reaches CSF concentrations above IC95. From a clinical point of view, the presence of Indinavir in CSF was associated with significant improvement of neurocognitive performances

Originator

Curator's Comment: # Merck & Co

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
47.9 µM [Ki]
0.37 nM [Ki]
100.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CRIXIVAN®

Approved Use

CRIXIVAN in combination with antiretroviral agents is indicated for the treatment of HIV infection.

Launch Date

1996
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
12617 nM
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
INDINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
17181 nM
500 mg/m² 3 times / day multiple, oral
dose: 500 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
INDINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
9231 nM × h
800 mg 3 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
INDINAVIR unknown
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
30691 nM × h
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
INDINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
38742 nM × h
500 mg/m² 3 times / day multiple, oral
dose: 500 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
INDINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
40%
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
INDINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2400 mg single, oral
Overdose
Dose: 2400 mg
Route: oral
Route: single
Dose: 2400 mg
Sources: Page: 20
unhealthy, adult
n = 23
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 23
Sources: Page: 20
Disc. AE: Renal disorders NEC, Gastrointestinal disorders NEC...
AEs leading to
discontinuation/dose reduction:
Renal disorders NEC (23 patients)
Gastrointestinal disorders NEC (23 patients)
Sources: Page: 20
1200 mg 2 times / day steady, oral
Higher than recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: steady
Dose: 1200 mg, 2 times / day
Sources: Page: 97
unhealthy, mean 42 years
n = 5
Health Status: unhealthy
Condition: HIV-1
Age Group: mean 42 years
Sex: M+F
Population Size: 5
Sources: Page: 97
Other AEs: Renal disorders NEC...
Other AEs:
Renal disorders NEC (5 patients)
Sources: Page: 97
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal disorders NEC 23 patients
Disc. AE
2400 mg single, oral
Overdose
Dose: 2400 mg
Route: oral
Route: single
Dose: 2400 mg
Sources: Page: 20
unhealthy, adult
n = 23
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 23
Sources: Page: 20
Renal disorders NEC 23 patients
Disc. AE
2400 mg single, oral
Overdose
Dose: 2400 mg
Route: oral
Route: single
Dose: 2400 mg
Sources: Page: 20
unhealthy, adult
n = 23
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 23
Sources: Page: 20
Renal disorders NEC 5 patients
1200 mg 2 times / day steady, oral
Higher than recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: steady
Dose: 1200 mg, 2 times / day
Sources: Page: 97
unhealthy, mean 42 years
n = 5
Health Status: unhealthy
Condition: HIV-1
Age Group: mean 42 years
Sex: M+F
Population Size: 5
Sources: Page: 97
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
weak
no (co-administration study)
Comment: Coadministration of quinidine sulfate (CYP2D6 inhibitor) did not significantly alter the pharmacokinetics of indinavir
Page: 145.0
yes
yes
yes (co-administration study)
Comment: Clarithromycin (500 mg q12h) increased the AUC of indinavir (800 mg q8h) by 29±42% and increased Cmax by 18±44%.
Page: 2.0
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Saquinavir soft gelatin capsule: a comparative safety review.
2001
Delavirdine: clinical pharmacokinetics and drug interactions.
2001
The emerging roles of non-nucleoside reverse transcriptase inhibitors in antiretroviral therapy.
2001
Virologic outcome and predictors of virologic failure of highly active antiretroviral therapy containing protease inhibitors.
2001 Apr
Smaller amounts of antiretroviral drugs are needed when combined with an active ribozyme against HIV-1.
2001 Apr
Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects.
2001 Apr
Gynecomastia associated with highly active antiretroviral therapy.
2001 Apr
Intracellular concentration of the HIV protease inhibitors indinavir and saquinavir in human endothelial cells.
2001 Apr
Long-term virologic and immunologic responses in human immunodeficiency virus type 1-infected children treated with indinavir, zidovudine, and lamivudine.
2001 Apr 1
Indinavir and systemic hypertension.
2001 Apr 13
Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport.
2001 Apr 13
Determination of serum levels of thirteen human immunodeficiency virus-suppressing drugs by high-performance liquid chromatography.
2001 Apr 13
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.
2001 Apr 15
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.
2001 Apr 15
Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy.
2001 Apr 15
[Didanosine as a capsule. A reliable drug in a new dosage form].
2001 Apr 2
[Acute porphyria and indinavir].
2001 Feb
[Long-term immunologic response in HIV-infected patients with CD4 cell counts
2001 Feb
Switch of protease inhibitor-containing HAART in routine clinical practice: a four-year prospective observational study.
2001 Feb
Sensitive and rapid method for the simultaneous quantification of the HIV-protease inhibitors indinavir, nelfinavir, ritonavir, and saquinavir in human plasma by reversed-phase liquid chromatography.
2001 Feb
Association between high serum prolactin levels and concomitant infections in HIV-infected patients.
2001 Feb
Human immunodeficiency virus (HIV) protease inhibitors have no effect on hepatitis C virus (HCV) serum levels of HIV-HCV co-infected patients.
2001 Feb
The absence of hyperbilirubinaemia is highly predictive of treatment failure in advanced HIV-infected patients treated with indinavir.
2001 Jan
Effect of alpha1-acid glycoprotein on the intracellular accumulation of the HIV protease inhibitors saquinavir, ritonavir and indinavir in vitro.
2001 Jan
Efficacy, tolerance, and pharmacokinetics of the combination of stavudine, nevirapine, nelfinavir, and saquinavir as salvage regimen after ritonavir or indinavir failure.
2001 Jan 20
Changes in host cell molecules acquired by circulating HIV-1 in patients treated with highly active antiretroviral therapy and interleukin-2.
2001 Jan 5
Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease.
2001 Jun
Severe lactic acidosis and thiamine administration in an HIV-infected patient on HAART.
2001 Jun
A comprehensive account on the role of efflux transporters in the gastrointestinal absorption of 13 commonly used substrate drugs in humans.
2001 Mar
HIV/AIDS case histories: indinavir crystalluria.
2001 Mar
The safety and antiviral effect of protease inhibitors in children.
2001 Mar
Resolution of microsporidial keratoconjunctivitis in an AIDS patient treated with highly active antiretroviral therapy.
2001 Mar
A retrospective, cohort-based survey of patients using twice-daily indinavir + ritonavir combinations: pharmacokinetics, safety, and efficacy.
2001 Mar 1
Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy.
2001 Mar 1
Indinavir, nevirapine, stavudine, and lamivudine for human immunodeficiency virus-infected, amprenavir-experienced subjects: AIDS Clinical Trials Group protocol 373.
2001 Mar 1
Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial.
2001 Mar 7
Assessment of active transport of HIV protease inhibitors in various cell lines and the in vitro blood--brain barrier.
2001 Mar 9
[Simultaneous quantitative determination of amprenavir and indinavir in human plasma by high-performance liquid chromatography].
2001 Mar-Apr
Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines.
2001 May
P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays.
2001 May
Residual human immunodeficiency virus type 1 infection in lymphoid tissue during highly active antiretroviral therapy: quantitation and virus characterization.
2001 May 1
Residual human immunodeficiency virus (HIV) Type 1 RNA and DNA in lymph nodes and HIV RNA in genital secretions and in cerebrospinal fluid after suppression of viremia for 2 years.
2001 May 1
Is indinavir crystalluria an indicator for indinavir stone formation?
2001 May 25
Low incidence of genotypic and phenotypic resistance in paediatric HIV-infected patients on long-term first-line antiretroviral triple therapy.
2001 May 25
'Do HIV-infected injecting drug users over-report adherence to highly active antiretroviral therapy?' A comparison between patients' self-reports and serum protease inhibitor concentrations in the French Manif 2000 cohort study.
2001 May 25
Sexual dysfunction associated with protease inhibitor containing highly active antiretroviral treatment.
2001 May 25
Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.
2001 May 25
Metabolic effects of indinavir in healthy HIV-seronegative men.
2001 May 4
Indinavir hair concentration in highly active antiretroviral therapy-treated patients: association with viral load and drug resistance.
2001 May 4
[Effective in HIV: dual combination with indinavir and ritonavir].
2001 May 4
Patents

Sample Use Guides

Usual Adult Dose for HIV Infection 800 mg orally every 8 hours or indinavir 800 mg plus ritonavir 100 to 200 mg orally every 12 hours
Route of Administration: Oral
Indinavir (10 nM) gave 14% inhibition of HIV replication alone and 81% in combination with P-gp/MRP inhibitors.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:03:37 GMT 2023
Edited
by admin
on Fri Dec 15 16:03:37 GMT 2023
Record UNII
9MG78X43ZT
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
INDINAVIR ANHYDROUS
Common Name English
(.ALPHA.R,.GAMMA.S,2S)-.ALPHA.-BENZYL-2-(TERT-BUTYLCARBAMOYL)-.GAMMA.-HYDROXY-N-((1S,2R)-2-HYDROXY-1-INDANYL)-4-(3-PYRIDYLMETHYL)-1-PIPERAZINEVALERAMIDE
Common Name English
indinavir [INN]
Common Name English
D-ERYTHRO-PENTONAMIDE, 2,3,5-TRIDEOXY-N-(2,3-DIHYDRO-2-HYDROXY-1H-INDEN-1-YL)-5-(2-(((1,1-DIMETHYLETHYL)AMINO)CARBONYL)-4-(3-PYRIDINYLMETHYL)-1-PIPERAZINYL)-2-(PHENYLMETHYL)-, (1(1S,2R),5(S))-
Common Name English
Indinavir [WHO-DD]
Common Name English
INDINAVIR [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175889
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
NCI_THESAURUS C97366
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
WHO-ATC J05AE02
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
NDF-RT N0000000246
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
Code System Code Type Description
EVMPD
SUB08174MIG
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
FDA UNII
9MG78X43ZT
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
MERCK INDEX
m6253
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY Merck Index
RXCUI
1546024
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY RxNorm
DRUG BANK
DB00224
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
DAILYMED
9MG78X43ZT
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
PUBCHEM
5362440
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
INN
7444
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
EPA CompTox
DTXSID4043802
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
CAS
150378-17-9
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
NCI_THESAURUS
C74585
Created by admin on Fri Dec 15 16:03:37 GMT 2023 , Edited by admin on Fri Dec 15 16:03:37 GMT 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SOLVATE->ANHYDROUS
EXCRETED UNCHANGED
Follow a single 1000 mg dose
AMOUNT EXCRETED
URINE
EXCRETED UNCHANGED
Follow a single 700 mg dose
AMOUNT EXCRETED
URINE
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC FASTED STATE

Biological Half-life PHARMACOKINETIC