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RALTEGRAVIR- FAMOUS INTEGRASE INHIBITOR

by Selleckchem | Jun 03 2012

INTEGRASE IN CASE OF HIV-1
The most deathly disease on earth, HIV-I, is being researched and studied a lot to find out an effective therapy against it. This virus contains some genes for enzymes/proteins and utilizes some others from the host cells. The enzyme in HIV that helps the virus to integrate its genome into host cell/genome is named as Integrase and gets replicated there. To search for the [roper treatment the first thing that must be keep in mind is resistance development by the mutation of their genes during replication, so it is the need of hour that the research about treatment of cancer must go on further and should be regularly updated. To inhibit their enzymatic activity is an attractive approach. The inhibitors for integrase enzyme have been developed and they inhibit the process of integration of viral genome into the host genome hence prevent its proliferation in the hosting cell. A huge wave of research is going on HIV-I regarding integrase inhibitors [1] that offer promising results against HIV-I virus [2]. Raltegravir integrase inhibitor is such an inhibitor that inhibits the integrase enzyme and it is the first inhibitor to get approved from FDA [3] and its discovery is no doubt considered to be a great blessing [4].

RALTEGRAVIR: PROPERTIES
Raltegravir structure shows that this inhibitor is actually a potassium salt that contains a single oxadiazole ring in its structure. For an oral administration, a mixture of Raltegravir is made in organic solvents as Raltegravir solubility is good in methanol, water, ethanol and DMSO. Merck pharmaceuticals are the manufacturers of Raltegravir and this company sales it under the brand name Isentress. Raltegravir price is around $200 for a 1 mg vial. All the physicians and the researchers can purchase Raltegravir from Raltegravir supplier according to their needs and purposes.
Raltegravir drug acts very rapidly and its effect is durable [5] that is why Raltegravir had been used for the treatment of HIV patients having already developed resistance [6]. Depositions tests for Raltegravir and its metabolic profile in the patients have exhibited impressing data results [7] when the quantification of metabolite was done in patient’s plasma [8] through High performance liquid chromatography technique or HPLC [9]. Not only in patients resistant for drug, Raltegravir has shown very efficacious results in case of herpes simplex virus [10]. Mode of action of Raltegravir involves the prevention of the integration of HIV-I genome into the genome of host cell by causing inhibition of enzyme involved in this process. Raltegravir is considered more valuable as compared to the other drugs against same organism [11]. Raltegravir in combination with Tenofovir has been analyzed and the synergistic effects were recorded in the therapy [12].

RALTEGRAVIR: CLINICAL TRIALS
Raltegravir was seen to have anti-HIV action against both treated resistant and naïve patients, therefore, this drug demands more study on it related to its pharmacokinetic properties to assess its safety, tolerability and efficacy [13]. Phase II Raltegravir clinical trial has shown that it reduces the viral replication in second phase very effectively [14]. Raltegravir has also been analyzed as a combinational therapeutic agent and it exhibited a very minimal interaction profile with the other drugs hence mitigating the demand for altering the dose of any other inhibitor molecule that is being used in combinational treatment [15]. Combinational therapy was analyzed in a trial period of 48 weeks to confirm the effects of all other drugs [16] and it was confirm by clinical trial phase II in a combinational treatment of Raltegravir with Etravirine, Ritonavir and Darunavir [17]. Raltegravir has been studied also to function solely and it showed remarkable results in phase I and phase III clinical trials [18]. When the resistance profile [20] of Raltegravir has been studied with multiple drug resistance virus [21] in clinical studies phase II, it is considered to be a best choice against same virus than using other inhibitors [19] and afterwards its dose kinetics was accordingly modified.

REFERENCES:
1. Savarino, A., A historical sketch of the discovery and development of HIV-1 integrase inhibitors. Expert Opin Investig Drugs, 2006.
2. Serrao, E.e.a., Raltegravir, elvitegravir, and metoogravir: the birth of "me-too" HIV-1 integrase inhibitors. Retrovirology, 2009.
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16. Markowitz, M.e.a., Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr., 2007.
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19. Lennox, J.L.e.a., Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. The Lancet, 2009.
20. Cooper, D.A.e.a., Subgroup and Resistance Analyses of Raltegravir for Resistant HIV-1 Infection. N Engl J Med, 2008.
21. Grinsztejn, B.e.a., Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. The Lancet, 2007.