Indinavir

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Indinavir
Indinavir structure.svg
Indinavir ball-and-stick.png
Systematic (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
Clinical data
Trade names Crixivan
AHFS/Drugs.com monograph
MedlinePlus a696028
Licence data US FDA:link
Pregnancy cat. C (US)
Legal status ?
Routes Oral
Pharmacokinetic data
Protein binding 60%
Metabolism Hepatic via CYP3A4
Half-life 1.8 (± 0.4) hours
Identifiers
CAS number 150378-17-9 YesY
ATC code J05AE02
PubChem CID 5362440
DrugBank DB00224
ChemSpider 4515036 YesY
UNII 9MG78X43ZT YesY
KEGG C07051 YesY
ChEBI CHEBI:44032 YesY
ChEMBL CHEMBL540914 N
NIAID ChemDB 005824
PDB ligand ID MK1 (PDBe, RCSB PDB)
Chemical data
Formula C36H47N5O4 
Mol. mass 613.79 g/mol
 N (what is this?)  (verify)

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

HIV-1 protease in complex with Indinavir. PDB entry 2avo[1]

History[edit]

The Food and Drug Administration (FDA) approved indinavir 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 resistant virus, such as lopinavir or atazanavir.

Administration[edit]

Unfortunately, indinavir wears off quickly after dosing, therefore requiring very precise dosing every eight hours in order 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.

Side effects[edit]

Most common side effects of indinavir include:[2]

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.[3]

Indinavir impairs endothelial function in healthy HIV-negative men and may accelerate atherosclerotic disease.[4]

References[edit]

  1. ^ Liu, F.; Boross, P. I.; Wang, Y. F.; Tozser, J.; Louis, J. M.; Harrison, R. W.; Weber, I. T. (2005). "Kinetic, Stability, and Structural Changes in High-resolution Crystal Structures of HIV-1 Protease with Drug-resistant Mutations L24I, I50V, and G73S". Journal of Molecular Biology 354 (4): 789–800. doi:10.1016/j.jmb.2005.09.095. PMC 1403828. PMID 16277992.  edit
  2. ^ "Crixivan® (indinavir sulfate) Capsules. Prescribing Information. Revised December 2013". Merck & Co., Inc. Retrieved 6 February 2014. 
  3. ^ M. Eira, M. Araujo and A.C. Seguro. Urinary NO3 excretion and renal failure in indinavir-treated patients. Brazilian Journal of Medical and Biological Research (2006) 39: 1065-1070.
  4. ^ Shankar SS, Dubé MP, Gorski JC, Klaunig JE, Steinberg HO. Indinavir impairs endothelial function in healthy HIV-negative men. Am Heart J. 2005 Nov;150(5):933.