Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:APRD00216 (ABC)
 8,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An advisory committee of the Food and Drug Administration (FDA) has recommended accelerated approval for abacavir (ABC, Ziagen). The approval decision was not unanimous due to concerns of drug toxicity. Three percent of those taking the drug have developed severe allergic reactions, and at least eight people have died of complications related to the allergic reaction. Abacavir works by attacking the viral enzyme reverse transcriptase (RT), and it is related to other drugs such as AZT, 3TC, d4T, ddI, and ddC. Abacavir should be taken twice daily, in combination with other anti-HIV medications.
 ...
PMID:Abacavir gets green light from FDA advisory board. Food and Drug Administration. 1136 24

The Food and Drug Administration (FDA) announced accelerated approval of Glaxo-Wellcome's abacavir (Ziagen, 1592) in combination with other antiretrovirals. Abacavir is in the same nucleoside analog class as AZT, but abacavir has stronger effects against HIV. Use of the drug requires caution, because it can cause a serious hypersensitivity or allergic reaction in 5 percent of patients. If abacavir is stopped and restarted, the hypersensitivity can be more fatal. Little is known about long-term use of the drug or its effects when in combination with other anti-HIV medications other than AZT plus 3TC.
 ...
PMID:Ziagen (abacavir) approved: caution essential. 1136 48

Information on dosage, cost, side effects, and interactions is provided for each of the seven nucleoside analog drugs available currently: Retrovir (AZT, ZDV), Videx (ddI), Hivid (ddC), Zerit (d4T), Epivir (3TC), Combivir (AZT/3TC), and Ziagen (abacavir sulfate). Most nucleoside analogs (with the exception of ddI) do not have food restrictions, but do have potential side effects such as nausea and fatigue. An activist, a doctor, and the drug's manufacturer offer comments. Contact information is provided.
 ...
PMID:What they say about nucleoside drugs. 1136 20

Available HIV drugs fall into three classes: nucleosides (nukes), non-nukes and protease inhibitors (PIs). Cross-resistance can occur, making all the drugs in a particular class ineffective for an individual. Therefore, doctors are choosing to use the fewest drugs possible for early treatment, saving other drugs for later therapy. Short-term results of triple therapy with three nukes (AZT, 3TC, and ABC (abacavir)) have been promising, especially among patients with little prior exposure to antiretroviral drugs. Thus some doctors are using triple nuke therapy in recently infected patients, and others with high CD4+ counts and low viral loads.
 ...
PMID:Nukes alone. 1136 32

In view of close similarities at the molecular and clinical levels, feline immunodeficiency virus (FIV) infection of the domestic cat is subject of increasing attention as an animal model for human immunodeficiency virus (HIV) infection. A range of reverse transcriptase inhibitors effective against HIV are also active against FIV, allowing successful use of the cat model to investigate drug interactions and resistance development. Nevertheless, while combined nucleoside analog and protease inhibitor usage has proven remarkably effective in treating HIV infection, combination antiretroviral therapy of FIV infection has been hampered by lack of protease inhibitors specific for FIV. In an attempt to circumvent this problem, we have examined the feasibility of applying in the FIV system combination protocols lacking a protease inhibitor. We now report that, as observed during HIV infection, the nucleoside analog abacavir (ABC or 1592U89) is able to effectively block in vitro FIV-replication. Furthermore, we demonstrate that combined usage of ABC with the nucleoside analogs zidovudine (ZDV or AZT) and lamivudine (3TC) also blocks in vitro FIV replication in a synergistic manner. However, in contrast to its effect on HIV replication, the ribonucleotide reductase inhibitor hydroxyurea (HU) is unable to effectively control in vitro FIV replication.
 ...
PMID:Combined effect of zidovudine (ZDV), lamivudine (3TC) and abacavir (ABC) antiretroviral therapy in suppressing in vitro FIV replication. 1168 14

The FDA approved FTC (emtricitabine, Emtriva) in July 2003 for use by adults in combination with other anti-HIV drugs. FTC is a nucleoside analog reverse transcriptase inhibitor (NRTI). Other drugs in this class include 3TC, abacavir, AZT, Combivir, d4T, d4T XR, ddC, ddI, ddI EC and Trizivir.
 ...
PMID:FTC (emtricitabine, Emtriva). 1469 67

Nucleoside and nucleotide analogues are essential for the design of effective antiretroviral regimens. There are currently many options for the selection of such drug backbones, although not all combinations will display optimal results. The concomitant administration of certain drugs should be avoided due to high rates of toxicity (ddl/d4T, ddl/TDF), antagonism (AZT/d4T, 3TC/FTC) and/or a greater risk of virological failure (ddl/TDF, ABC/TDF). The understanding of the plasmatic and intracellular metabolism of nucleoside/nucleotide analogues is crucial for deciding the optimal posology of each drug and the better dual combinations to be selected. Interferences between the pathways involved into the intracellular activation of some nucleoside/nucleotide analogues may help to understand why certain drug combinations should be avoided.
 ...
PMID:Combinations of nucleoside/nucleotide analogues for HIV therapy. 1570 Jun 22

An immunological comparison of three different third companions (abacavir [ABC], efavirenz [EFV], ritonavir-boosted indinavir [IDVr]) on a backbone of either zidovudine plus didanosine (AZT/ddI) or zidovudine plus lamivudine (AZT/3TC) was performed in 76 HIV-infected, advanced-naive patients. Baseline median CD4 count and viremia were 217/microL and 238,301 copies/mL, respectively. Immunologic parameters were measured at baseline and after months of therapy. By the end of the study, 36 patients (mostly in the protease inhibitor [PI]-containing arms) had dropped out of the study; 22/36 cases of drop out were due to tolerability issues. All regimens resulted in increases in CD4 counts, with the most solid changes seen in patients using ABC as a third companion. Median HIV plasma viremia at month 12 was <50 copies/mL, and viremia was undetectable in 26/38 patients (68%). At the end of the study period, HIV antigen- and mitogen-stimulated proliferation overall was better in patients using either of the PI-boosted third companions. In these patients, the strongest down-modulation of activation marker-bearing cells was also observed. Finally, CD8+/28-/CD45RA+ lymphocytes (effector cells) were increased in all groups of patients with the exception of individuals receiving PI-boosted therapies. Results of this pilot study, although very preliminary, suggest that different combinations of antivirals result in a range of effects on immune cell functions. The clinical implications of these results need to be further analyzed in follow-up studies and in larger cohorts of patients.
 ...
PMID:An immunological comparison of third companion in advanced drug-naive HIV-infected patients. 1716 15

Experiments were performed to investigate the impact of didanosine (ddI), lamivudine (3TC), and stavudine (d4T) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using a cell cloning assay for assessing the effects of individual nucleoside analogs (NRTIs)/drug combinations in human TK6 B-lymphoblastoid cells. Three-day treatments with 0, 33, 100, or 300 microM ddI, 3TC, or ddI-3TC produced positive trends for increased HPRT and TK mutant frequencies. While dose-related trends were too small to reach significance after treatments with d4T or d4T-3TC, pairwise comparisons with control cells indicated that exposure to 100 microM d4T or d4T-3TC caused significant elevations in HPRT mutants. Measurements of mutagenicity in cells exposed to d4T (or d4T-3TC) were complicated by the cytotoxicity of this NRTI. Enhanced increases in mutagenic responses to combined NRTI treatments, compared with single drug treatments, occurred as additive to synergistic effects in the HPRT gene of cells exposed to 100 microM ddI-3TC or 100 microM d4T-3TC, and in the TK gene of cells exposed to 100 or 300 microM ddI-3TC. Comparisons of these data to mutagenicity studies of other NRTIs in the same system (Meng Q et al. [2000c]: Proc Natl Acad Sci USA 97:12667-126671; Torres SM et al. [2007]: Environ Mol Mutagen) indicate that the relative mutagenic potencies for all drugs tested to date are: AZT-ddI > ddI-3TC > AZT-3TC congruent with AZT-3TC-ABC (abacavir) > AZT >/=ddI > d4T-3TC > 3TC > d4T >/= ABC. These collective data suggest that all NRTIs with antiviral activity against HIV-1 may cause host cell DNA damage and mutations, and impose a cancer risk.
 ...
PMID:Relative mutagenic potencies of several nucleoside analogs, alone or in drug pairs, at the HPRT and TK loci of human TK6 lymphoblastoid cells. 1735 29

Nucleoside analogs used in antiretroviral treatment have been associated with mitochondrial toxicity. The polymerase-gamma hypothesis states that this toxicity stems from the analogs' inhibition of the mitochondrial DNA polymerase (polymerase-gamma) leading to mitochondrial DNA (mtDNA) depletion. We have constructed a computational model of the interaction of polymerase-gamma with activated nucleoside and nucleotide analog drugs, based on experimentally measured reaction rates and base excision rates, together with the mtDNA genome size, the human mtDNA sequence, and mitochondrial dNTP concentrations. The model predicts an approximately 1000-fold difference in the activated drug concentration required for a 50% probability of mtDNA strand termination between the activated di-deoxy analogs d4T, ddC, and ddI (activated to ddA) and the activated forms of the analogs 3TC, TDF, AZT, FTC, and ABC. These predictions are supported by experimental and clinical data showing significantly greater mtDNA depletion in cell culture and patient samples caused by the di-deoxy analog drugs. For zidovudine (AZT) we calculated a very low mtDNA replication termination probability, in contrast to its reported mitochondrial toxicity in vitro and clinically. Therefore AZT mitochondrial toxicity is likely due to a mechanism that does not involve strand termination of mtDNA replication.
 ...
PMID:An analysis of enzyme kinetics data for mitochondrial DNA strand termination by nucleoside reverse transcription inhibitors. 1913 79


1 2 Next >>