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Raltegravir
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| Systematic (IUPAC) name | |
| N-(2-(4-(4-fluorobenzylcarbamoyl)
-5-hydroxy-1-methyl-6-oxo-1, 6-dihydropyrimidin-2-yl)propan-2-yl) -5-methyl-1,3,4-oxadiazole-2- carboxamide |
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| Identifiers | |
| CAS number | |
| ATC code | J05 |
| PubChem | |
| Chemical data | |
| Formula | C20H21FN6O5 |
| Mol. mass | 444.42 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | 83% |
| Metabolism | Hepatic (UGT1A1) |
| Half life | 9 hours |
| Excretion | feces and urine |
| Therapeutic considerations | |
| Licence data |
, |
| Pregnancy cat. |
C(US) |
| Legal status | |
| Routes | oral |
Raltegravir (MK-0518, brand name Isentress) is an antiretroviral drug produced by Merck & Co, used to treat HIV infection. It received FDA approval in October 2007, the first of a new class of HIV drugs, the integrase inhibitors, to receive such approval.
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Mechanism
Raltegravir targets integrase, an HIV enzyme that integrates the viral genetic material into human chromosomes, a critical step in the pathogenesis of HIV. Raltegravir, and other integrase inhibitors, are often termed strand transfer inhibitors. This refers to the process of DNA strand transfer from the viral genome to the host genome. The drug is metabolized away via glucuronidation.1
Dosage
Raltegravir is taken orally twice daily. Doses of 200, 400, and 600 mg have been studied.
At the 2007 Conference on Retroviruses and Opportunistic Infections, researchers presented Phase III data showing that 77% of patients taking the 400 mg dose of raltegravir plus other antiretroviral drugs reached HIV viral loads below 400 copies, nearly twice as many compared with a control group.
Indications
Raltegravir is approved only for use in individuals whose infection has proven resistant to other HAART drugs. As with any HAART medication, Raltegravir is unlikely to show durability if used as monotherapy.
Efficacy
In a study of the drug as part of combination therapy, raltegravir exhibited potent and durable antiretroviral activity similar to that of efavirenz at 24 and 48 weeks but achieved HIV-1 RNA levels below detection at a more rapid rate. After 24 and 48 weeks of treatment, raltegravir did not result in increased serum levels of total cholesterol, low-density lipoprotein cholesterol, or triglycerides.23
Research
Raltegravir significantly alters HIV viral dynamics and decay and further research in this area is ongoing. In clinical trials patients taking Raltegravir achieved viral loads less than 50 copies per millitre sooner than those taking similarly potent Non-nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors. This statistically significant difference in viral load reduction has caused some HIV researchers to begin questioning long held paradigms about HIV viral dynamics and decay. 4 Research into Raltegravir's ability to affect latent viral reservoirs and possibly aid in the eradication of HIV is currently ongoing. 5
Research results were published in the New England Journal of Medicine on July 24, 2008. The authors concluded that "raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks." 6
References
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This article's citation style may be unclear. The references used may be clearer with a different or consistent style of citation, footnoting, or external linking. (April 2008) |
- Savarino A (December 2006). "A historical sketch of the discovery and development of HIV-1 integrase inhibitors". Expert Opin Investig Drugs 15 (12): 1507–22. doi:. PMID 17107277, http://www.ingentaconnect.com/content/apl/eid/2006/00000015/00000012/art00004?token=00461400d664264f65263a3d4f58762f467c405847447b23442f5f31256f5b20655d3b.
- ^ HIV Antiretroviral Agents in Development - The Body
- ^ Markowitz M, Nguyen BY, Gotuzzo E, et al (2007). "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. 46 (2): 125–33. doi:. PMID 17721395, http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?doi=10.1097/QAI.0b013e318157131c.
- ^ Stephenson J (2007). "Researchers buoyed by novel HIV drugs: will expand drug arsenal against resistant virus". JAMA 297 (14): 1535–6. doi:. PMID 17426263, http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=17426263.
- ^ Faster Viral Decay With Raltegravir - The Body
- ^ ClinicalTrials.gov NCT00554398 Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
- ^ Steigbigel RT, Cooper DA, Kumar PN, et al (July 2008). "Raltegravir with optimized background therapy for resistant HIV-1 infection". N. Engl. J. Med. 359 (4): 339–54. doi:. PMID 18650512, http://content.nejm.org/cgi/content/abstract/359/4/339.
External links
- Manufacturer's website
- MK-0518 at Aidsmedscom
- Integrase Inhibitor Raltegravir (MK-0518) Doubles HIV Suppression in Treatment-Experienced Patients (Aidsmap 28 February 2007)
- RMK-0518 Abstract from CROI 2007
- Interim Results From Phase II Study Of MK-0518
- World patent covering the potassium salt
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Wikipedia content modification information:
- This page was last modified on 5 November 2008, at 19:29.
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