Entecavir
From Wikipedia, the free encyclopedia
 |
This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please improve this article by introducing more precise citations where appropriate. (March 2008) |
 |
|
|
Entecavir
|
|
| Systematic (IUPAC) name | |
| 2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-6,9-dihydro-3H-purin-6-one | |
| Identifiers | |
| CAS number | |
| ATC code | J05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C12H15N5O3 |
| Mol. mass | 277.279 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | 13% |
| Metabolism | ? |
| Half life | 128–149 hours |
| Excretion | Renal 62–73% |
| Therapeutic considerations | |
| Licence data | |
| Pregnancy cat. |
C(US) |
| Legal status | |
| Routes | Oral |
Entecavir (INN) (pronounced /ɛnˈtɛkəvɪr/) is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade name Baraclude (BMS).
Entecavir is a nucleoside analog[1] (more specifically, a guanine analogue) that inhibits reverse transcription, DNA replication and transcription in the viral replication process. The drug's manufacturer claims that entecavir is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir).
Entecavir was approved by the U.S.FDA in March 2005.
[edit] History
1992: SQ-34676 at Squibb as part of anti-herpes virus program11. 1997: BMS 200475 developed at BMS pharmaceutical research institute as antiviral nucleoside analogue à Activity demonstrated against HBV, HSV-1, HCMV, VZV in cell lines & no or little activity against HIV or influenza12,13.
Superior activity observed against HBV pushed research towards BMS 200475, its base analogues and its enantiomer against HBV in HepG2.2.15 cell line12 Comparison to other NAs, proven more selective potent inhibitor of HBV by virtue of being Guanine NA13 1998: Inhibition of hepadnaviral polymerases was demonstrated in vitro in comparison to a number of NAs-TP14.
Metabolic studies showed more efficient phosphorylation to triphosphate active form15.
3 year treatment of woodchuck model of CHB sustained antiviral efficacy and prolonged life spans without detectable emergence of resistance16.
Efficacy # LVD resistant HBV replication in vitro17. Superior activity compared to LVD invivo for both HBeAg + & HBeAg- patients18, 19. Efficacy in LVD refractory CHB patients20.
[edit] References
- ^ Sims KA, Woodland AM (December 2006). "Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection". Pharmacotherapy 26 (12): 1745–57. doi:. PMID 17125436. http://www.atypon-link.com/doi/abs/10.1592/phco.26.12.1745.
11. Slusarchyk, W. A., A. K. Field, J. A. Greytok, P. Taunk, A. V. Tooumari, M. G. Young, and R. Zahler. 4-Hydroxy-3-(hydroxymethyl)-2-methylcyclopentyl purines and pyrimidines, a novel class of anti-herpesvirus agents. Abstract from the Fifth International Conference on Antiviral Research. Antivir Res 1992.17(Suppl. 1):98. 12. Bisacchi, G. S., S. T. Chao, C. Bachard, J. P. Daris, S. F. Innaimo, J. A. Jacobs, O. Kocy, P. Lapointe, A. Martel, Z. Merchant, W. A. Slusarchyk, J. E. Sundeen, M. G. Young, R. Colonno, and R. Zahler. BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro. Bioorg. Med. Chem. Lett. 1997. 7:127–132. 13. Innaimo S F, Seifer M, Bisacchi G S, Standring D N, Zahler R, Colonno R J. Identification of BMS-200475 as a Potent and Selective Inhibitor of Hepatitis B Virus. Antimicrob. Agents Chemother. 1997. 41(7): 1444–1448. 14. Seifer, M., R. K. Hamatake, R. J. Colonno, and D. N. Standring. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob. Agents Chemother. 1998. 42:3200–3208. 15. Yamanaka, G., T. Wilson, S. Innaimo, G. S. Bisacchi, P. Egli, J. K. Rinehart, R. Zahler, and R. J. Colonno. Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus. Antimicrob. Agents Chemother. 1999. 43:190–193. 16. Colonno, R. J., E. V. Genovesi, I. Medina, L. Lamb, S. K. Durham, M. L. Huang, L. Corey, M. Littlejohn, S. Locarnini, B. C. Tennant, B. Rose, and J. M. Clark. Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection. J. Infect. Dis. 2001.184:1236–1245. 17. Levine, S., D. Hernandez, G. Yamanaka, S. Zhang, R. Rose, S. Weinheimer, and R. J. Colonno. Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. Antimicrob. Agents Chemother. 2002.46:2525–2532. 18. Chang, T. T. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N. Engl. J. Med. 2006. 354:1001–1010. 19. Lai, C. L. et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N. Engl. J.Med. 2006. 354:1011–1020. 20. Sherman, M., C. Yurdaydin, J. Sollano, M. Silva, Y. F. Liaw, J. Cianciara, A. Boron-Kaczmarska, P. Martin, Z. Goodman, R. J. Colonno, A. Cross, G. Denisky, B. Kreter, R. Hindes, and the AI463026 Behold Study Group. Entecavir for the treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006. 130:2039–2049. 21. Tenney D J et al. Two-Year Assessment of Entecavir Resistance in Lamivudine-Refractory Hepatitis B Virus Patients Reveals Different Clinical Outcomes Depending on the Resistance Substitutions Present. Antimicrob Agents Chemother. 2007, 51: 902–911. 22. Langley DR, Tenney DJ, et al. Inhibition of Hepatitis B Virus Polymerase by Entecavir. Virology. 2007. 81(8):3992–4001. 23. McMahon M A, et al. The HBV Drug Entecavir — Effects on HIV-1 Replication and Resistance. N Engl J Med 2007. 356:2614-21. 24. Hirsch M S. Entecavir Surprise. N Engl J Med 2007. 356(25): 2641-2643.
[edit] External links
 |
This pharmacology-related article is a stub. You can help Wikipedia by expanding it. |
|
||||||||||||||||||||||||||||||||||||||||||||||
