Raltegravir

From Wikipedia, the free encyclopedia

Raltegravir
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
Identifiers
CAS number	871038-72-1
ATC code	J05AX08
PubChem	11598201
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	EU, US
Pregnancy cat.	C(US)
Legal status	POM(UK) ℞-only(US)
Routes	oral

Raltegravir (MK-0518, brand name Isentress^TM) 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.

Contents 1 Mechanism 2 Dosage 3 Indications 4 Efficacy 5 Research 6 References 7 External links

[edit] 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]

[edit] 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.

[edit] Indications

Raltegravir is approved only for use only 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.

[edit] 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.^[2][3]

[edit] 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 then 50 copies per millitre sooner then those taking similarly potent Non-nucleoside Reverse Transcriptinase 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]

[edit] References

The references in this article would be clearer with a different or consistent style of citation, footnoting, or external linking.

[edit] 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

v • d • e Merck & Co., Inc. Corporate Directors: Richard Clark · Johnnetta Cole · William Harrison · William Kelley · Rochelle Lazarus · Thomas Shenk · Anne Tatlock · Samuel Thier · Wendell Weeks · Peter Wendell Products: Alendronate · Aprepitant · Ertapenem · Ezetimibe · Ezetimibe/simvastatin · Finasteride · Fosaprepitant · Indinavir · Losartan · Lovastatin · Montelukast · Raltegravir · Rizatriptan · Rofecoxib · Simvastatin · Sitagliptin · Vorinostat Publications: The Merck Index · The Merck Manual Annual Revenue: $22.9 billion USD (▲2% FY 2004) · Employees: 63,000 · Stock Symbol: NYSE: MRK · Website: www.merck.com

v • d • e Antivirals used against HIV (HAART) (primarily J05) Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI) Abacavir (ABC)° • Emtricitabine° • Lamivudine (3TC)° • Tenofovir° • Didanosine • Zidovudine (AZT) • Apricitabine† • Stampidine† • Elvucitabine† • Racivir† • Amdoxovir† • Stavudine‡ • Zalcitabine‡ Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) Efavirenz° • Nevirapine • Etravirine • Rilpivirine† • Loviride‡ • Delavirdine‡ Protease Inhibitors (PI) Atazanavir° • Fosamprenavir° • Lopinavir° • Darunavir • Nelfinavir • Ritonavir • Saquinavir • Tipranavir • Amprenavir‡ • Indinavir‡ Entry/fusion inhibitors Enfuvirtide • Maraviroc • Vicriviroc† • PRO 140† • Ibalizumab† Integrase inhibitors Raltegravir • Elvitegravir† Maturation inhibitors Bevirimat† • Vivecon™† Combined formulations Combivir • Atripla • Trizivir • Truvada • Kaletra • Epzicom Other & experimental agents Foscarnet • Hydroxyurea • Synergistic enhancers • Epigallocatechin gallate • Portmanteau inhibitors • Globoidnan A • Griffithsin • Diarylpyrimidines • Calanolide A • Cyanovirin-N • Miltefosine • R-roscovitine† °DHHS preferred first-line agent. †Undergoing clinical trials, not FDA approved. ‡Formerly or rarely used agent.