|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Pregnancy cat.||C (US)|
|Metabolism||Hepatic via CYP3A4|
|Half-life||1.8 (± 0.4) hours|
|Mol. mass||613.79 g/mol|
|(what is this?)|
The Food and Drug Administration (FDA) approved indinavir March 13, 1996, making it the eighth approved antiretroviral. Indinavir was 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.
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.
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"
Endothelial cells produce nitric oxide (NO) which causes blood vessels to dilate, lowers blood pressure, allows oxygen to reach and nutrients to reach tissues, and allows carbon dioxide and metabolic waste to be removed. Nitric oxide is highly reactive and quickly reacts with molecular oxygen (O2) to form nitrogen dioxide (NO2).
- 2NO + O2 → 2NO2
A further reaction between nitrogen dioxide (NO2) and water (H2O) can produce nitrate (NO3). The nitrate is then removed from the body in the urine. The kidney is filled with small blood vessels. In the absence of nitric oxide, these blood vessels may become constricted, and the kidney may become ischemic, leading to kidney disease.
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.
- 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.
- "Crixivan® (indinavir sulfate) Capsules. Prescribing Information. Revised December 2013". Merck & Co., Inc. Retrieved 6 February 2014.
- 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.