Indinavir

{{Drugbox | Verifiedfields = changed | verifiedrevid = 477168143 | IUPAC_name = (2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-4-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamoyl}butyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide | image = Indinavir structure.svg | width = 251 | image2 = Indinavir ball-and-stick.png

| tradename = Crixivan | Drugs.com = Monograph | MedlinePlus = a696028 | licence_US = Indinavir | pregnancy_US = C | legal_status = | routes_of_administration = Oral

| bioavailability = ~65% | protein_bound = 60% | metabolism = Hepatic via CYP3A4 | elimination_half-life = 1.8 ± 0.4 hours

| CAS_number_Ref =  ^Y | CAS_number = 150378-17-9 | ATC_prefix = J05 | ATC_suffix = AE02 | ATC_supplemental = | PubChem = 5362440 | DrugBank_Ref =  ^Y | DrugBank = DB00224 | ChemSpiderID_Ref =  ^Y | ChemSpiderID = 4515036 | NIAID_ChemDB = 005824 | UNII_Ref =  ^Y | UNII = 9MG78X43ZT | KEGG_Ref =  ^Y | KEGG = C07051 | ChEBI_Ref =  ^Y | ChEBI = 44032 | ChEMBL_Ref =  ^N | ChEMBL = 540914 | PDB_ligand = MK1

| C=36 | H=47 | N=5 | O=4 | molecular_weight = 613.79 g/mol | smiles = 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 | StdInChI_Ref =  ^Y | StdInChI = 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 | StdInChIKey_Ref =  ^Y | StdInChIKey = CBVCZFGXHXORBI-PXQQMZJSSA-N }}

Indinavir (IDV; trade name Crixivan, manufactured by Merck) is a protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS.

HIV-1 protease in complex with indinavir. PDB entry 2avo

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.

Medical uses

Unfortunately, indinavir wears off quickly after dosing, so requires very precise dosing every eight hours to thwart HIV from forming drug-resistant mutations, including resistances to other protease inhibitors. It has restrictions on what sorts of food may be eaten concurrently. For these reasons it is now rarely used.

Side effects

The most common side effects of indinavir include:

• Gastrointestinal disturbances (abdominal pain, diarrhea, nausea, vomiting)
• General malaise and fatigue
• Nephrolithiasis/urolithiasis (the formation of kidney stones), which sometimes may lead to more severe condition including kidney failure
• Metabolic alterations including hyperlipidemia (cholesterol or triglyceride elevations) and hyperglycemia
• Alterations in body shape (lipodystrophy), colloquially known as "Crix belly"

Indinavir inhibits urinary nitrous oxide production and may inhibit nitric oxide production. Treatment with this drug is frequently associated with renal abnormalities, sterile leukocyturia, and reduced creatinine clearance.

Indinavir impairs endothelial function in healthy HIV-negative men and may accelerate atherosclerotic disease.

History

The Food and Drug Administration approved indinavir on March 13, 1996, making it the eighth approved antiretroviral. Indinavir is much more powerful than any prior antiretroviral drug; using it with dual NRTIs set the standard for treatment of HIV/AIDS and raised the bar on design and introduction of subsequent antiretroviral drugs. Protease inhibitors changed the very nature of the AIDS epidemic from one of a terminal illness to a somewhat manageable one.

Increasingly, it is being replaced by newer drugs that are more convenient to take and less likely to promote virus resistance, such as darunavir or atazanavir.