Palinavir

Palinavir is a protease inhibitor used in the treatment of HIV/AIDS. It is part of the class of antiretroviral drugs that inhibit the action of the HIV-1 protease, an enzyme critical for the maturation of infectious viral particles. By inhibiting this enzyme, Palinavir prevents the cleavage of the gag-pol polyprotein, resulting in the production of immature, non-infectious viral particles.

Mechanism of Action

Palinavir works by binding to the active site of the HIV-1 protease enzyme, thereby blocking its activity. This inhibition prevents the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins required for the assembly of a mature virion. As a result, the virus is unable to replicate effectively within the host cells.

Pharmacokinetics

Palinavir is administered orally and has a bioavailability of approximately 70%. It is extensively metabolized in the liver, primarily by the cytochrome P450 enzyme system, particularly CYP3A4. The drug has a half-life of about 6-8 hours, necessitating twice-daily dosing to maintain therapeutic levels. It is excreted primarily in the feces, with a small percentage eliminated via the urine.

Clinical Use

Palinavir is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children. It is often used as part of a highly active antiretroviral therapy (HAART) regimen. The drug is effective in reducing viral load and increasing CD4 cell counts, thereby improving immune function and reducing the risk of opportunistic infections.

Adverse Effects

Common side effects of Palinavir include gastrointestinal disturbances such as nausea, vomiting, and diarrhea. It may also cause lipodystrophy, a condition characterized by changes in body fat distribution. Other potential adverse effects include hyperlipidemia, insulin resistance, and hepatotoxicity. Patients on Palinavir should be monitored regularly for these side effects.

Drug Interactions

Palinavir is known to interact with a variety of other medications, primarily due to its metabolism by the CYP3A4 enzyme. 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 decrease the effectiveness of Palinavir by increasing its clearance.

Resistance

Resistance to Palinavir can develop through mutations in the HIV-1 protease gene. These mutations can reduce the binding affinity of the drug to the enzyme, thereby diminishing its inhibitory effect. Resistance testing is recommended for patients experiencing virologic failure on a regimen containing Palinavir.

Also see

• HIV/AIDS
• Protease inhibitor
• Antiretroviral therapy
• Cytochrome P450
• Drug resistance in HIV