Elvucitabine
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| Non-proprietary name | Elvucitabine | |||||||||||||||
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| Molecular formula | C 9 H 10 FN 3 O 3 | |||||||||||||||
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| Molar mass | 227.19 g · mol -1 | |||||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||
Elvucitabine ( ACH-126,443 ) is an experimental drug for the treatment of HIV -infected patients as part of an HIV combination therapy and an HBV infection.
Elvucitabine is a cytidine analogue and belongs to the group of nucleoside reverse transcriptase inhibitors (NRTIs).
history
Elvucitabine was developed by Achillion Pharmaceuticals . A study with patients with lamivudine (Epivir) or emtricitabine (Emtriva) resistance and simultaneous M184 mutation was terminated in 2007. It is currently unclear whether the substance will be further developed at all. The last release is from 2011.
pharmacology
Elvucitabine is an enantiomer of dexelvucitabine (reverse) and is also effective against HIV and HBV . Phase II studies in HIV and HBV are currently ongoing. In HIV patients with the M184V mutation , a small, double-blind study showed a drop in viral load of 0.7–0.8 log levels after 28 days. The study was discontinued, however, because leukopenia developed in 6/56 patients taking 100 mg elvucitabine .
Comparative studies with Epivir suggest that the suppressive effect of elvucitabine is slightly weaker (0.3 logs on average).
The mitochondrial toxicity appears to be lower than with dexelvucitabine. Current results show that the binding affinity for reverse transcriptase-resistant viruses may also be lower.
Pharmacokinetics
Studies have found an extremely long half-life of 150 hours. Against this background, a once-daily dose seems very likely.
Side effects
The apparently low mitochondrial toxicity was positive in studies. One study had to be discontinued, however, because leukopenia occurred in 6/56 patients with 100 mg elvucitabine . Some patients also developed rashes . On the other hand, pancreatitis as seen with dexelvucitabine does not appear to occur.
Resistances
In-vitro it was shown to be effective against various NRTI resistances. The selection of viruses with their own resistances such as M184I or the previously completely unknown mutant D237E was observed. The selection of these specific resistances under HAART will probably not be observed.
Web links
Individual evidence
- ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
- ↑ a b c Entry Elvucitabine ( Memento of the original from March 21, 2008 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. on aidsmeds.com.
- ^ RK Ghosh, SM Ghosh, S. Chawla: Recent advances in antiretroviral drugs. In: Expert opinion on pharmacotherapy. Volume 12, number 1, January 2011, pp. 31-46, doi : 10.1517 / 14656566.2010.509345 , PMID 20698725 .
- ↑ M. Desai, G. Iyer, RK Dikshit: Antiretroviral drugs: critical issues and recent advances. In: Indian journal of pharmacology. Volume 44, number 3, May 2012, pp. 288-298, doi : 10.4103 / 0253-7613.96296 , PMID 22701234 , PMC 3371447 (free full text).
- ↑ a b Dark LM. et al. (2003): Elvucitabine: potent antiviral activity demonstrated in multidrug-resistant HIV infection . In: Antiviral Therapy 8: S5.
- ↑ Murakami E. et al. (2004): Investigating the effects of stereochemistry on incorporation and removal of 5-fluorocytidine analogs by mitochondrial DNA polymerase gamma: comparison of D- and L-D4FC-TP . In: Antiviral Res . 62 (1); 57-64, PMID 15026203 .
- ↑ Colucci P, Pottage J, Robison H, et al. The different clinical pharmacology of elvucitabine (beta-L-Fd4C) enables the drug to be given in a safe and effective manner with innovative drug dosing. Abstract LB-27, 45th ICAAC 2005, Washington.
- ↑ Dunkle LM, Oshana1 SC, Cheng YC, et al .: ACH-126,443: a new nucleoside analog with potent activity against wild type and resistant HIV-1 and a promising pharmacokinetic and mitochondrial safety profile ( Memento of the original from August 21, 2009 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . Abstract 303, 8th CROI 2001, Chicago.
- ↑ Fabrycki J. et al. (2003): In vitro induction of HIV variants with reduced susceptibility to elvucitabine (ACH-126,443, beta-L-Fd4C). Antiviral Therapy 8: S8.
