Indinavir
Clinical data | |
---|---|
Trade names | Crixivan |
AHFS/Drugs.com | Monograph |
MedlinePlus | a696028 |
License data | |
Pregnancy category |
|
Routes of administration |
Oral |
ATC code | J05AE02 (WHO) |
Pharmacokinetic data | |
Bioavailability | ~65% |
Protein binding | 60% |
Metabolism | Hepatic via CYP3A4 |
Biological half-life | 1.8 ± 0.4 hours |
Identifiers | |
CAS Number | 150378-17-9 |
PubChem | CID 5362440 |
DrugBank | DB00224 |
ChemSpider | 4515036 |
UNII | 9MG78X43ZT |
KEGG | C07051 |
ChEBI | CHEBI:44032 |
ChEMBL | CHEMBL540914 |
NIAID ChemDB | 005824 |
PDB ligand ID | MK1 (PDBe, RCSB PDB) |
Chemical and physical data | |
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
|
|
3D model (Jmol) | Interactive image |
Formula | C36H47N5O4 |
Molar mass | 613.79 g/mol |
|
|
|
|
(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 to treat HIV/AIDS.
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.[2]
Medical uses[edit]
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[edit]
The most common side effects of indinavir include:[3]
- 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"[4]
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.[5]
Indinavir impairs endothelial function in healthy HIV-negative men and may accelerate atherosclerotic disease.[6]
History[edit]
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.
References[edit]
- ^ 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.
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ "Crixivan® (indinavir sulfate) Capsules. Prescribing Information. Revised December 2013" (PDF). Merck & Co., Inc. Retrieved 6 February 2014.
- ^ "Protease inhibitors' metabolic side effects: cholesterol, triglycerides, blood sugar, and "Crix belly"". AIDS Treatment News (277): 1–4. 1997. PMID 11364559.
- ^ 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.
- ^ 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.