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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^[1]

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

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:^[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

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

^ 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.

UpToDate Contents

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English Journal

Indanes-Properties, Preparation, and Presence in Ligands for G Protein Coupled Receptors.

Vilums M1, Heuberger J1, Heitman LH1, IJzerman AP1.
Medicinal research reviews.Med Res Rev.2015 Nov;35(6):1097-126. doi: 10.1002/med.21352. Epub 2015 May 27.
The indane (2,3-dihydro-1H-indene) ring system is an attractive scaffold for biologically active compounds due to the combination of aromatic and aliphatic properties fused together in one rigid system. This bicyclic structure provides a wide range of possibilities to incorporate specific substituen
PMID 26018667

Cover Image, Volume 36, Issue 25.

[No authors listed]
Journal of computational chemistry.J Comput Chem.2015 Sep 30;36(25):i-ii. doi: 10.1002/jcc.24056.
HIV-1 protease (PR) is a promising drug target for anti-HIV therapy. However, the susceptibility of PR to mutation has reduced the efficacy of protease inhibitors (PIs), such as indinavir, as a viable anti-HIV drug. On page 1885 (DOI: 10.1002/jcc.24020), Dawei Zhang and coworkers use molecular dynam
PMID 26311441

Understanding the basis of I50V-induced affinity decrease in HIV-1 protease via molecular dynamics simulations using polarized force field.

Duan R1, Lazim R1, Zhang D1.
Journal of computational chemistry.J Comput Chem.2015 Sep 30;36(25):1885-92. doi: 10.1002/jcc.24020. Epub 2015 Jul 22.
Human immunodeficiency virus (HIV)-1 protease is one of the most promising drug target commonly utilized to combat Acquired Immune Deficiency Syndrome (AIDS). However, with the emergence of drug resistance arising from mutations, the efficiency of protease inhibitors (PIs) as a viable treatment for
PMID 26198456

Related Pictures

CRIXIVAN Crixivan Capsules | NPS MedicineWise HIV / AIDS / Generic Crixivan (Indinavir Crixivan (indinavir) Drug Side Effects Crixivan, Crixivan opinie, Crixivan ulotka Drugs reference index « Crixivan »

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「インジナビル」

Indinavir
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
License data	US FDA: Indinavir;
Pregnancy; category	US: C (Risk not ruled out); ;
Routes of; administration	Oral
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
ATC code	J05AE02 (WHO)
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 data
Formula	C36H47N5O4
Molar mass	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 ;
	InChI 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 ; Key:CBVCZFGXHXORBI-PXQQMZJSSA-N ;
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英: indinavir, IDV
商: Crixivan、クリキシバン

[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.

[2] "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[3] "Crixivan^® (indinavir sulfate) Capsules. Prescribing Information. Revised December 2013" (PDF). Merck & Co., Inc. Retrieved 6 February 2014.

[4] "Protease inhibitors' metabolic side effects: cholesterol, triglycerides, blood sugar, and "Crix belly"". AIDS Treatment News (277): 1–4. 1997. PMID 11364559.

[5] 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.

[pmid16290967-6] 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.

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Crixivan