Crixivan

Crixivan

Crixivan is the brand name for the antiretroviral drug indinavir, which is used in the treatment of HIV/AIDS. It belongs to a class of drugs known as protease inhibitors, which play a crucial role in the management of HIV infection by inhibiting the action of the protease enzyme, thereby preventing viral replication.

Mechanism of Action

Crixivan works by binding to the active site of the HIV protease enzyme. This enzyme is essential for the cleavage of viral polyproteins into functional proteins, which are necessary for the assembly of new virions. By inhibiting this enzyme, Crixivan prevents the maturation of the virus, resulting in the production of non-infectious viral particles.

Pharmacokinetics

Indinavir is administered orally and is rapidly absorbed from the gastrointestinal tract. It is recommended to be taken on an empty stomach or with a light meal to enhance absorption. The drug is extensively metabolized in the liver by the cytochrome P450 enzyme system, particularly CYP3A4. The half-life of indinavir is approximately 1.8 hours, necessitating frequent dosing to maintain effective plasma concentrations.

Clinical Use

Crixivan is used in combination with other antiretroviral agents as part of Highly Active Antiretroviral Therapy (HAART) for the treatment of HIV-1 infection. It is not used as monotherapy due to the rapid development of resistance.

Side Effects

Common side effects of Crixivan include:

• Nephrolithiasis (kidney stones)
• Hyperbilirubinemia
• Gastrointestinal disturbances such as nausea and diarrhea
• Lipodystrophy

Patients are advised to maintain adequate hydration to reduce the risk of kidney stones.

Drug Interactions

Crixivan is known to interact with several other medications due to its metabolism by CYP3A4. It can increase the plasma concentrations of drugs that are also metabolized by this enzyme, leading to potential toxicity. Conversely, drugs that induce CYP3A4 can reduce the effectiveness of indinavir.

Resistance

Resistance to indinavir can develop through mutations in the protease gene of HIV. This can lead to cross-resistance with other protease inhibitors, making it crucial to use Crixivan as part of a combination therapy to minimize the risk of resistance.

History

Crixivan was approved by the Food and Drug Administration (FDA) in 1996 and was one of the first protease inhibitors to be used in the treatment of HIV/AIDS. It played a significant role in the transformation of HIV from a fatal disease to a manageable chronic condition.

See Also

• HIV/AIDS
• Protease inhibitor
• Highly Active Antiretroviral Therapy

References

• Hammer, S. M., et al. (1997). "A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less." New England Journal of Medicine, 337(11), 725-733.
• Gulick, R. M., et al. (1997). "Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy." New England Journal of Medicine, 337(11), 734-739.