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RALTEGRAVIR- AN INTEGRASE INHIBITOR

by Selleckchem | Apr 27 2012

INTEGRASE AND HIV-1
HIV-I, one of the deathly diseases present on earth, is being researched a lot in order to find an efficacious therapy against it. The virus contains some of the genes for proteins/enzymes and utilizes some from the host. Integrase is one of the enzymes present in virus that helps it to integrate its genome into the host genome and get itself replicated there. In order to search for the treatment, first thing that is kept in mind is the development of resistance by getting their genes mutated during replication, therefore it is need of the hour that research on the treatment against cancer must go on and should be updated. Inhibiting the enzymatic activity is one of the approaches. Inhibitors of integrase have also been developed that inhibit the integration of genome of the virus into that of the host and therefore prevent it to proliferate inside the host cell. A lot of research is going on HIV-I in the area of integrase inhibitors [1] which offer new promises in for therapy against HIV-I [2]. Raltegravir integrase inhibitor is one of such inhibitors and the first one to get approval from FDA [3] and the discovery of which is considered a blessing [4].

PROPERTIES OF RALTEGRAVIR
Raltegravir is potassium salt and contains an oxadiazole ring in it. Raltegravir solubility in organic solvents can be achieved for making it a mixture for oral administration e.g., it is soluble in water, methanol, DMSO, and ethanol. It has been developed by Merck pharmaceutical company and the brand name under which it is sold is Isentress. For 1 mg Raltegravir price is approximately $200. Researchers or physicians can buy Raltegravir for their own purposes.
Raltegravir acts rapidly and its action is durable [5] therefore it had been used for treating HIV patients who had developed resistance [6]. The metabolic profile of the drug in patient and its deposition tests have showed impressing data [7] when the metabolite was quantified in the plasma [8] of patients through HPLC (High performance liquid chromatography) [9]. Nor only in drug resistant patients, Raltegravir has also shown efficacious results against herpes virus [10]. Mechanism of action of the drug involves prevention of the HIV-I genome integration into the host genome by inhibiting the enzyme involved in the process. This drug is considered more efficacious as compared to other drugs present against similar organism [11]. Combination of Raltegravir and Tenofovir has been studied and synergistic effects have been seen in the treatment [12].

CLINICAL TRIALS OF THE DRUG
Raltegravir was observed to have anti-HIV activity against naïve and treated resistant patients both, therefore, it demands more research related to its pharmacokinetics in order to assess its efficacy, safety and tolerability [13]. It has been studied in Raltegravir clinical trial phase II that the drug effectively reduces viral replication in its second phase [14]. The drug has also been studied in combination therapy and it showed a profile of minimal interaction with other drugs therefore mitigating the need to alter the dose of any of the inhibitors used in the combinatorial treatment [15]. Combinatorial therapy was observed in a 48 weeks of trial period in order to confirm the effects of all the drugs [16] and was confirmed by phase II clinical trial in a combinatorial therapy of Raltegravir with Darunavir or Ritonavir and Etravirine [17]. Raltegravir has also been studied to function singly where it showed long term efficacious results in clinical trial phase I and III [18]. It has been considered to be better choice than other inhibitors against the same virus [19] when its resistance profile has been studied [20] in clinical trial phase II with MDR Multiple drug resistance virus [21] and afterwards dose kinetics was modified accordingly.

REFERENCES:
1. Savarino, A., A historical sketch of the discovery and development of HIV-1 integrase inhibitors. Expert Opin Investig Drugs, 2006.
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