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Drug Class: Nucleoside Reverse Transcriptase Inhibitors
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Drug Description |
| Elvucitabine, or ELV, is an L-cytosine nucleoside analogue of stavudine with potent activity against HIV.[1][2] |
HIV/AIDS-Related Uses |
| Elvucitabine is a nucleoside reverse transcriptase inhibitor (NRTI) currently under investigation in Phase II/III trials for the treatment of chronic HIV infection and infection by lamivudine-resistant HIV.[3] |
Non HIV/AIDS-Related Uses |
| Elvucitabine exhibits potent activity against hepatitis B virus (HBV). A Phase I/II study of elvucitabine in patients with chronic HBV infection demonstrated acceptable pharmacokinetics and safety profiles. Phase II studies of elvucitabine in chronically HBV infected patients are underway.[4][5] |
Dosing Information |
Mode of Delivery |
| Oral.[6] |
Dosage Form |
| In clinical trials, dosages studied include 5 and 10 mg once daily and 20 mg once every other day.[7][8] |
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Pharmacology |
Elvucitabine is a beta-L-(-) nucleoside analogue developed to improve upon the antiviral activity of lamivudine, an FDA-approved beta-L-(-) nucleoside analogue. Compared with lamivudine, elvucitabine may allow for less frequent dosing and less escalation of dosage to overcome viral resistance.[9] Elvucitabine, a stavudine-substituted NRTI, has potent antiretroviral activity, even at doses low enough to avoid bone marrow toxicity.[10][11] Elvucitabine inhibits wild-type HIV and HIV expressing the M184V mutation associated with lamivudine resistance.[12]
Elvucitabine has excellent oral bioavailability and a prolonged half-life of more than 100 hours.[13][14][15]
When elvucitabine dosages of 5 or 10 mg once daily or 20 mg once every other day were tested in 24 HIV infected patients for 21 days with concomitant lopinavir/ritonavir (LPV/r) every 12 hours, viral load decreased 1.8, 1.9, and 2.0 log, respectively. Elvucitabine's extended half-life required continuation of LPV/r doses for 35 days total in the 10 and 20 mg cohorts. Concentrations of elvucitabine remained above the 50% inhibitory concentration (IC50) at Day 28, supporting weekly or twice-weekly dosing. The every-other-day cohort appeared most efficacious and minimized resistance and adherence concerns.[16] |
Adverse Events/Toxicity |
Elvucitabine induces bone marrow toxicity when used at dosages higher than elvucitabine 50 mg daily. Preliminary study results reported at the 12th International HIV Drug Resistance Workshop in June 2003 indicated that elvucitabine induced reversible bone marrow suppression. Six of 56 patients experienced myelosuppression while taking elvucitabine; of these six patients, four received 100 mg daily and two received 50 mg daily. Mild to moderate macropapular rash occurred with the 50 and 100 mg doses but resolved with drug discontinuation. Mild headache and gastrointestinal distress were also reported.[17][18]
For 21 days at dosages of elvucitabine 5 and 10 mg once daily and 20 mg once every other day, no bone marrow suppression was observed, and elvucitabine was generally nontoxic.[19] |
Drug And Food Interactions |
| The half-life of elvucitabine was approximately 150 hours when administered with LPV/r. Elvucitabine exhibited decreased bioavailability and slower absorption rates with concomitant LPV/r but was otherwise unchanged.[20] |
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Clinical Trials |
| Click here to search ClinicalTrials.gov for trials that use Elvucitabine. |
Chemistry |
CAS Name |
| 2(1H)-Pyrimidinone, 4-amino-1-((2S,5R)-2,5-dihydro-5-[21] |
CAS Number |
| 181785-84-2[22] |
Molecular Formula |
| C9-H10-F-N3-O3[23] |
Elemental Composition |
| C47.8%, H4.4%, F8.0%, N18.6%, O21.2%[24] |
Molecular Weight |
| 226[25] |
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Further Reading |
PMID/11966452 Chen, SH. Comparative evaluation of L-Fd4C and related nucleoside analogs as promising antiviral agents. Curr Med Chem. 2002 May;9(9):899-912.
PMID/15105115 Dutschman GE, Grill SP, Gullen EA, Haraguchi K, Takeda S, Tanaka H, Baba M, Cheng YC. Novel 4'-substituted stavudine analog with improved anti-human immunodeficiency virus activity and decreased cytotoxicity. Antimicrob Agents Chemother. 2004 May;48(5):1640-6.
PMID/12476956 Patel J, Mitra AK. ACH-126443 Achillion/Yale University. Curr Opin Investig Drugs. 2002 Nov;3(11):1580-4. Review.
Study of Once Daily Elvucitabine Versus Lamivudine in Subjects With a Documented M184V Mutation. Available at: http://www.clinicaltrials.gov/ct/NCT00312039. Accessed 08/03/06.
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Manufacturer Information |
Elvucitabine
Achillion Pharmaceuticals
300 George Street
New Haven, CT 06511
(202) 624-7000
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References |
[1] Natap.org - The Different Clinical Pharmacology of Elvucitabine (B-L-Fd4C) Enables the Nuke Drug to be Given in a Safe and Effective Manner with Innovative Dosing Regimens. Conference Reports, December 18, 2005. Available at: http://www.natap.org/2005/ICAAC/icaac_20.htm. Accessed 08/03/06.
[2] Antimicrob Agents Chemother - 2004 May;48(5):1640-6
[3] Achillion Pharmaceuticals - Pipeline: HIV Program - Elvucitabine. Available at: http://www.achillion.com/beta.php. Accessed 08/03/06.
[4] Natap.org - The Different Clinical Pharmacology of Elvucitabine (B-L-Fd4C) Enables the Nuke Drug to be Given in a Safe and Effective Manner with Innovative Dosing Regimens. Conference Reports, December 18, 2005. Available at: http://www.natap.org/2005/ICAAC/icaac_20.htm. Accessed 08/03/06.
[5] ClinicalTrials.gov - Safety and Antiviral Activity Study of ACH-126,443 (Beta-L-Fd4C) in Treatment-Naive Adults With Chronic Hepatitis B Virus Infection. Available at: http://www.clinicaltrials.gov/ct/NCT00034359. Accessed 08/03/06.
[6] Achillion Pharmaceuticals - Pipeline: HIV Program - Elvucitabine. Available at: http://www.achillion.com/beta.php. Accessed 08/03/06.
[7] Achillion Pharmaceuticals - Pipeline: HIV Program - Elvucitabine. Available at: http://www.achillion.com/beta.php. Accessed 08/03/06.
[8] HIV and Hepatitis.com - Pharmacology of Elvucitabine Enables Innovative Dosing Regimens. Coverage of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, January 13, 2006. Available at: http://www.hivandhepatitis.com/2005icr/icaac/docs/011306_a.html. Accessed 08/03/06.
[9] Antimicrob Agents Chemother - 1998 Jul;42(7):1799-804
[10] HIV and Hepatitis.com - Pharmacology of Elvucitabine Enables Innovative Dosing Regimens. Coverage of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, January 13, 2006. Available at: http://www.hivandhepatitis.com/2005icr/icaac/docs/011306_a.html. Accessed 08/03/06.
[11] Antimicrob Agents Chemother - Antimicrob Agents Chemother - 2004 May;48(5):1640-6
[12] Achillion Pharmaceuticals - Pipeline: HIV Program - Elvucitabine. Available at: http://www.achillion.com/beta.php. Accessed 08/03/06.
[13] Conf Retroviruses Opportunistic Infect - 8th. 2001. Abstract 303.
[14] International HIV Drug Resistance Workshop - 12th. 2003.
[15] Natap.org - The Different Clinical Pharmacology of Elvucitabine (B-L-Fd4C) Enables the Nuke Drug to be Given in a Safe and Effective Manner with Innovative Dosing Regimens. Conference Reports, December 18, 2005. Available at: http://www.natap.org/2005/ICAAC/icaac_20.htm. Accessed 08/03/06.
[16] HIV and Hepatitis.com - Pharmacology of Elvucitabine Enables Innovative Dosing Regimens. Coverage of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, January 13, 2006. Available at: http://www.hivandhepatitis.com/2005icr/icaac/docs/011306_a.html. Accessed 08/03/06.
[17] International HIV Drug Resistance Workshop - 12th. 2003.
[18] HIV and Hepatitis.com - Pharmacology of Elvucitabine Enables Innovative Dosing Regimens. Coverage of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, January 13, 2006. Available at: http://www.hivandhepatitis.com/2005icr/icaac/docs/011306_a.html. Accessed 08/03/06.
[19] Natap.org - The Different Clinical Pharmacology of Elvucitabine (B-L-Fd4C) Enables the Nuke Drug to be Given in a Safe and Effective Manner with Innovative Dosing Regimens. Conference Reports, December 18, 2005. Available at: http://www.natap.org/2005/ICAAC/icaac_20.htm. Accessed 08/03/06.
[20] Medscape - Pharmacology of Investigational Antiretroviral Drugs: CCR5 Inhibitors. Available at: http://www.medscape.com/viewarticle/505544. Accessed 08/03/06.
[21] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 08/03/06
[22] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 08/03/06
[23] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 08/03/06.
[24] Calculation. -
[25] Calculation. -
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Updated August 3, 2006
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