Индинавир: История, Свойства и Ограничения Применения

Chemical compound
Indinavir (IDV; trade name Crixivan, made by Merck) is a protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS. It is soluble white powder administered orally in combination with other antiviral drugs. The drug prevents protease from functioning normally. Consequently, HIV viruses cannot reproduce, causing a decrease in the viral load. Commercially sold indinavir is indinavir anhydrous, which is indinavir with an additional amine in the hydroxyethylene backbone. This enhances its solubility and oral bioavailability, making it easier for users to intake. It was synthetically produced for the purpose of inhibiting the protease in the HIV virus. Currently, it is not recommended for use in HIV/AIDS treatment due to its side effects. Furthermore, it is controversial for many reasons starting from its development to its usage. It was patented in 1991 and approved for medical use in 1996.

Indinavir does not cure HIV/AIDS, but it can extend the length of a person's life for several years by slowing the progression of the disease. The type that is widely used and created by Merck is indinavir sulfate. The pills are created from sulfate salts and are sold in dosages of 100, 200, 333, and 400 mg of indinavir. It is normally used as one of the three drugs in a triple combination therapy for the HIV virus.]] Indinavir wears off quickly after dosing. Unboosted indinavir requires a very precise dosing of 400 mg every eight hours to thwart HIV from forming drug resistant mutations, including resistances to other protease inhibitors. Boosted indinavir requires two 400 mg indinavir capsules with 1 to 2 100 mg ritonavir capsules twice a day. In both cases, the drugs must be taken with plenty of water one or two hours after a meal. It is recommended that users drink at least 1.5 liters a day when intaking the drug. Drug users must significantly increase their water intake due to indinavir's low solubility that can cause it to crystallize. There are restrictions on what sorts of food may be eaten concurrently with the unboosted indinavir treatment. Furthermore, it is no longer recommended to use in the United States for initial treatments due to pill burden and risk of kidney stones.

Indinavir is a white crystalline powder. It is very soluble in water and methanol. Each capsule contains sulfate salt in addition to anhydrous lactose and magnesium stearate. The capsule shell is made of gelatin and titanium dioxide. Its melting point or its temperature of decomposition is 150 153 °C at which it starts to emit toxic vapors such as nitrogen oxides and sulfur oxides. A couple months later on January, 1987, a team of researchers consisting of Emilio Emini, Joel Huff, and Irving Sigal, kickstarted their studies by basing their project off of earlier research on the protease enzyme, renin. They were the ones who started the process of research and development into protease inhibitors and its relation to the virus. Over a year later, in July 1988, Nancy Kohl, Emilio Emini, et al., published in the Proceedings of the National Academy of the Science about the idea of inhibiting the protease. The results of the study showed that the most effective treatment was the three drug treatment. After 24 weeks of treatment, 24 patients of the 28 patients who were treated with the three drugs were able to have viral load levels have less than 500 copies/ml. 12 out of 28 patients under indinavir monotherapy reached 500 copies/ml, and none of the thirty patients in AZT and lamivudine group got below 500 copies. After 38 weeks, 6% of the people in the three drug group died while 11% of the people died in the two drug group. There were higher CD4 cell counts and less viral load in patients assigned to the three drug group, proving that a three drug treatment is more efficient than a two drug one.

Because of its limited supply, Merck decided to adopt a single distributor system in which they would send indinavir to only one pharmaceutical retail company. They sold it to Stadtalnder's Pharmacy and limited quantities to Veteran Administration's hospitals and some managed care organizations. This caused prices to be raised and limited the number of people who could have access to this possibly life saving drug.

Indinavir cost about $12 for a daily dose, which is 24% less than Invirase and 33% less than Norvir. Because the company used a single distributor system to sell their drugs, the retail price was marked up 37% by the pharmacy that sold it. In response to this hefty price, Merck stated that it cost a lot to research and develop the drug, and they did not have enough supplies to sell it through a normal distributor system. Activists protested against this price because it made it harder for people to have access to the drug.