INDINAVIR

US Previously Marketed

First approved in 1996

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C36H47N5O4.H2O
Molecular Weight	631.8048
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.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=XTYSXGHMTNTKFH-BDEHJDMKSA-N

InChI=1S/C36H47N5O4.H2O/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);1H2/t28-,29+,31+,32-,33+;/m1./s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00224
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
UDP-glucuronosyltransferase 1-1 15 Target ID: CHEMBL1287617 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16118329	Inhibitor 8297	47.9 µM [Ki]
Human immunodeficiency virus type 1 protease 35 Target ID: CHEMBL243 Sources: http://www.drugbank.ca/drugs/DB00224	Inhibitor 8297	0.37 nM [Ki]
Leishmania amazonensis 8 Target ID: CHEMBL612877 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22579524	Inhibitor 8297	100.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV infection 21 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf	Primary		Approved 8429	CRIXIVAN® Approved Use CRIXIVAN in combination with antiretroviral agents is indicated for the treatment of HIV infection. Launch Date 1996

C_max

Value	Dose	Co-administered	Analyte	Population
12617 nM DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	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

Value	Dose	Analyte	Population
9231 nM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
40% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	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

Dose	Population	Adverse events
2400 mg single, oral Overdose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20	unhealthy, adult n = 23 Health Status: unhealthy Condition: HIV-1 Age Group: adult Sex: unknown Population Size: 23 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf 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: https://pubmed.ncbi.nlm.nih.gov/10513637/ 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: https://pubmed.ncbi.nlm.nih.gov/10513637/ Page: 97	Other AEs: Renal disorders NEC... Other AEs: Renal disorders NEC (5 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10513637/ Page: 97

AEs

AE	Significance	Dose	Population
Gastrointestinal disorders NEC	23 patients Disc. AE	2400 mg single, oral Overdose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20	unhealthy, adult n = 23 Health Status: unhealthy Condition: HIV-1 Age Group: adult Sex: unknown Population Size: 23 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20	unhealthy, adult n = 23 Health Status: unhealthy Condition: HIV-1 Age Group: adult Sex: unknown Population Size: 23 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf 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: https://pubmed.ncbi.nlm.nih.gov/10513637/ 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: https://pubmed.ncbi.nlm.nih.gov/10513637/ Page: 97

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2E1 882 CYP2B6 810	P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	weak
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	yes	yes (co-administration study) Comment: in the same study, clarithromycin AUC was increased by 53 ±36% and Cmax increased 22 ± 33% following coadministration with indinavir. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020685Orig1s000rev.pdf#page=145 Page: 145.0	weak	no (co-administration study) Comment: Coadministration of quinidine sulfate (CYP2D6 inhibitor) did not significantly alter the pharmacokinetics of indinavir Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020685Orig1s000rev.pdf#page=145 Page: 145.0
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9435299/ Page: -	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=2 Page: 2.0	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%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=2 Page: 2.0

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0207	http://www.3bsc.com/index/pro_info.php?id=19563
AA Blocks	AA001MH2	https://www.aablocks.com/goods/Goods/detail?id=AA001MH2
AHH Chemical co.,ltd	API-1193	http://www.ahhchemical.com/product/API-1193.html
AK Scientific, Inc. (AKSCI)	69104	http://www.aksci.com/item_detail.php?cat=69104
Aurora Fine Chemicals LLC	A13.111.810	http://online.aurorafinechemicals.com/info?ID=A13.111.810
AvaChem Scientific	2152B	http://www.avachem.com/productSearch.asp?2152B
BLD Pharm	BD134557	http://www.bldpharm.com/products/150378-17-9.html
BioSynth	J-008694	https://www.biosynth.com/en/products/all-products/products/J-008694.html
CSNpharm	CSN11198	https://www.csnpharm.com/products/indinavir.html
Chem Scene	CS-2930	http://www.chemscene.com/150378-17-9.html
ChemMol	30107683	http://www.chemmol.com/chemmol/30107683.html
ChemMol	99047026	http://www.chemmol.com/chemmol/99047026.html
Chemspace	CSSB00000053661	https://chem-space.com/CSSB00000053661
DC Chemicals	DC8906	http://www.dcchemicals.com/product_show-Indinavir.html
Glentham Life Sciences	GP8542	http://www.glentham.com/products/product/GP8542/
Hairui	HR130052	http://www.hairuichem.com/en/product/150378-17-9.html
Lab Network	LN00202000	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00202000
Matrix Scientific	99281	https://www.matrixscientific.com/099281.html
MedChem Express	HY-B0689	https://www.medchemexpress.com/indinavir.html
OChem	7422	http://www.ocheminc.com/index.php?act=psearch&pid=378I179
Parchem	29155	http://www.parchem.com/chemical-supplier-distributor/Indinavir-019155.aspx
Smolecule	S530618	http://www.smolecule.com/products/s530618
THE BioTek	bt-271014	https://www.thebiotek.com/product/inhibitors/bt-271014
Yuhao Chemical	RT5885	http://www.chemyuhao.com/150378-17-9.html
eNovation Chemicals	D591373	https://www.enovationchem.com/ProductDetails.asp?ProductID=D591373
eNovation Chemicals	D674369	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674369
iChemical	EBD41965	http://www.ichemical.com/chemicals/cas-150378-17-9

PubMed

Title	Date	PubMed
Saquinavir soft gelatin capsule: a comparative safety review.	2001	11347724
Comparison of P-triglyceride levels among patients with human immunodeficiency virus on randomized treatment with ritonavir, indinavir or ritonavir/saquinavir.	2001	11345223
The emerging roles of non-nucleoside reverse transcriptase inhibitors in antiretroviral therapy.	2001	11217868
Gynecomastia associated with highly active antiretroviral therapy.	2001 Apr	11302408
Intracellular concentration of the HIV protease inhibitors indinavir and saquinavir in human endothelial cells.	2001 Apr	11266428
Long-term virologic and immunologic responses in human immunodeficiency virus type 1-infected children treated with indinavir, zidovudine, and lamivudine.	2001 Apr 1	11237839
Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport.	2001 Apr 13	11371681
Determination of serum levels of thirteen human immunodeficiency virus-suppressing drugs by high-performance liquid chromatography.	2001 Apr 13	11355843
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.	2001 Apr 15	11391173
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.	2001 Apr 15	11391165
Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy.	2001 Apr 15	11304769
[Didanosine as a capsule. A reliable drug in a new dosage form].	2001 Apr 2	11373794
[Acute porphyria and indinavir].	2001 Feb	11275609
[Long-term immunologic response in HIV-infected patients with CD4 cell counts	2001 Feb	11240420
Switch of protease inhibitor-containing HAART in routine clinical practice: a four-year prospective observational study.	2001 Feb	11236109
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	11206045
[Anti-infection prophylaxis after sexual assault. Experience of the Raymond Poincaré-Garches Hospital].	2001 Feb 17	11252969
[Bilateral hip necrosis, corticoids, and human immunodeficiency virus protease inhibitors].	2001 Jan	11256248
Economic analysis of initial HIV treatment. Efavirenz- versus indinavir-containing triple therapy.	2001 Jan	11252549
The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study.	2001 Jan 26	11216928
New developments in anti-HIV chemotherapy.	2001 Jan-Feb	11347962
The HIV protease inhibitor indinavir decreases insulin- and contraction-stimulated glucose transport in skeletal muscle.	2001 Jun	11375341
The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance.	2001 Jun	11375339
Hypercholesterolemia in a health care worker receiving thyroxine after postexposure prophylaxis for human immunodeficiency virus infection.	2001 Jun 1	11340537
The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design.	2001 Jun 15	11396919
A comprehensive account on the role of efflux transporters in the gastrointestinal absorption of 13 commonly used substrate drugs in humans.	2001 Mar	11396754
Incidence and clinical relevance of the interactions and side effects of Hypericum preparations.	2001 Mar	11315759
HIV/AIDS case histories: indinavir crystalluria.	2001 Mar	11313030
Effect of indinavir on the pharmacokinetics of rifampicin in HIV-infected patients.	2001 Mar	11291758
The safety and antiviral effect of protease inhibitors in children.	2001 Mar	11253853
Resolution of microsporidial keratoconjunctivitis in an AIDS patient treated with highly active antiretroviral therapy.	2001 Mar	11239874
A retrospective, cohort-based survey of patients using twice-daily indinavir + ritonavir combinations: pharmacokinetics, safety, and efficacy.	2001 Mar 1	11242194
Competition prompts drug companies to cut antiretroviral drug prices.	2001 Mar 17	11265962
Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors.	2001 Mar 30	11316998
Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial.	2001 Mar 7	11231744
Assessment of active transport of HIV protease inhibitors in various cell lines and the in vitro blood--brain barrier.	2001 Mar 9	11242145
[Simultaneous quantitative determination of amprenavir and indinavir in human plasma by high-performance liquid chromatography].	2001 Mar-Apr	11282520
Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors.	2001 May	11322888
Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines.	2001 May	11316764
P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays.	2001 May	11297905
Residual human immunodeficiency virus type 1 infection in lymphoid tissue during highly active antiretroviral therapy: quantitation and virus characterization.	2001 May 1	11375053
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	11294662
Treatment of primary human immunodeficiency virus type 1 infection with potent antiretroviral therapy reduces frequency of rapid progression to AIDS.	2001 May 15	11319682
Is indinavir crystalluria an indicator for indinavir stone formation?	2001 May 25	11400000
Low incidence of genotypic and phenotypic resistance in paediatric HIV-infected patients on long-term first-line antiretroviral triple therapy.	2001 May 25	11399999
'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	11399998
Sexual dysfunction associated with protease inhibitor containing highly active antiretroviral treatment.	2001 May 25	11399984
Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.	2001 May 25	11399982
Metabolic effects of indinavir in healthy HIV-seronegative men.	2001 May 4	11399973
Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma by high-performance liquid chromatography.	2001 May 5	11393736

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

Indinavir (10 nM) gave 14% inhibition of HIV replication alone and 81% in combination with P-gp/MRP inhibitors.

Name

Type

Language

INDINAVIR

Official Name

English

INDINAVIR [USP-RS]

Common Name

English

INDINAVIR [USAN]

Common Name

English

(αR,γS,2S)-α-Benzyl-2-(tert-butylcarbamoyl)-γ-hydroxy-N-[(1S,2R)-2-hydroxy-1-indanyl]-4-(3-pyridylmethyl)-1-piperazinevaleramide monohydrate

Common Name

English

INDINAVIR SYSTEM SUITABILITY [USP-RS]

Common Name

English

Indinavir monohydrate [WHO-DD]

Common Name

English

INDINAVIR SYSTEM SUITABILITY

Common Name

English

INDINAVIR MONOHYDRATE

Common Name

English

INDINAVIR [VANDF]

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)-, MONOHYDRATE, (1(1S,2R),5(S))-

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548674