Apricitabine: A Novel Deoxycytidine Analogue Nucleoside Reverse Transcriptase Inhibitor for the Treatment of Nucleoside-Resistant HIV Infection
| dc.contributor.author | Wainberg, Mark A | |
| dc.contributor.author | Cahn, Pedro | |
| dc.contributor.author | Bethell, Richard C | |
| dc.contributor.author | Sawyer, James | |
| dc.contributor.author | Cox, Susan | |
| dc.date.accessioned | 2024-05-23T23:49:04Z | |
| dc.date.available | 2024-05-23T23:49:04Z | |
| dc.date.issued | 2007-04 | |
| dc.description | Fil: Cahn P. Fundación Huésped, Buenos Aires; Argentina | es_ES |
| dc.description.abstract | Existing nucleoside reverse transcriptase inhibitors for HIV disease are limited by problems of resistance and, in some cases, long-term toxicity. Apricitabine (ATC; formerly BCH10618, SPD754 and AVX754) is a deoxycytidine analogue nucleoside reverse transcriptase inhibitor in clinical development. ATC retains substantial in vitro activity against HIV-1 containing many mutations associated with nucleoside reverse transcriptase inhibitor resistance, showing a less than twofold reduction in susceptibility in the presence of either up to five thymidine analogue mutations or the M184V mutation. ATC showed a low potential for cellular or mitochondrial toxicity in vitro. ATC is well absorbed orally, with a bioavailability of 65–80%. Its plasma elimination half-life (approximately 3 h), and the intracellular half-life of its triphosphate (TP) metabolite (6–7 h) support twice-daily dosing. Intracellular ATC-TP levels are markedly reduced in the presence of lamivudine or emtricitabine, indicating that clinical co-administration of ATC together with these agents will not be possible. The drug is renally eliminated, giving a low potential for hepatic drug interactions. In a double-blind, randomized, placebo-controlled Phase II monotherapy trial in antiretroviral-naive patients, ATC doses of 1,200 and 1,600 mg/day reduced plasma viral load levels by 1.65 and 1.58 log10 HIV RNA copies/ml, respectively, after 10 days of treatment (P<0.0001 versus placebo). ATC showed a low propensity to select for resistance mutants in vitro and during clinical monotherapy. ATC was well tolerated in volunteers and in HIV-infected patients. This promising profile suggests that ATC may be useful in treating patients who have failed previous lamivudine- or emtricitabine-containing regimens. Further studies to evaluate the long-term efficacy and tolerability of ATC are underway. | es_ES |
| dc.format | application/pdf | es_ES |
| dc.identifier.doi | https://doi.org/10.1177/095632020701800201 | |
| dc.identifier.uri | https://repositorio.huesped.org.ar/handle/123456789/1305 | |
| dc.language | ENG | es_ES |
| dc.provenance | Published | es_ES |
| dc.relation.ispartofseries | Antiviral Chemistry and Chemotherapy;2007;18(2):61-70 | |
| dc.rights | openAccess | es_ES |
| dc.subject | Deoxycytidine | es_ES |
| dc.subject | HIV | es_ES |
| dc.title | Apricitabine: A Novel Deoxycytidine Analogue Nucleoside Reverse Transcriptase Inhibitor for the Treatment of Nucleoside-Resistant HIV Infection | es_ES |
| dc.type | Articulo | es_ES |