Apricitabine does not select additional drug resistance mutations in tissue culture in HIV-1 variants containing K65R, M184V or M184V plus thymidine analogue mutations. Human immunodeficiency virus type 1 containing the reverse transcriptase mutation M184V or K65R or mutations M41L, M184V, and T215Y did not accumulate additional resistance mutations in the reverse transcriptase when increasing amounts of apricitabine drug pressure were applied. The original mutations were maintained by the presence of apricitabine but were lost when cultured without drug pressure.
Apricitabine: a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of nucleoside-resistant HIV infection. 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
Effect of Lamivudine on the plasma and intracellular pharmacokinetics of apricitabine, a novel nucleoside reverse transcriptase inhibitor, in healthy volunteers. Apricitabine is a novel deoxycytidine analog reverse transcriptase inhibitor. In vitro apricitabine competes with other deoxycytidine analogues for intracellular phosphorylation mediated by deoxycytidine kinase. The topic of this study , the effect of concomitant administration of apricitabine and lamivudine on the plasma and intracellular pharmacokinetics of the two compounds, was investigated in healthy volunteers. Participants (n = 21; age, 18 to 30 years) received apricitabine at 600 mg twice daily, lamivudine at 300 mg once daily, and the two treatments in combination for 4 days each in random order. Plasma, urine, and intracellular
Influence of food on the pharmacokinetics of apricitabine, a novel deoxycytidine analogue reverse transcriptase inhibitor. Apricitabine is a novel deoxycytidine analogue reverse transcriptase inhibitor with clinical efficacy against both wild-type and drug-resistant HIV. The objective of this study was to evaluate the influence of feeding on apricitabine absorption and plasma pharmacokinetics . Twenty healthy, male, HIV-negative volunteers were recruited for this randomised, open-label, crossover study and administered 1200 mg apricitabine orally either following fasting or a high-fat meal. Multiple blood samples were collected over a time course between 0 and 36 h following dosing, and plasma apricitabine concentration was measured using liquid chromatography-tandem mass spectrometry
Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients. Apricitabine (formerly AVX754 and SPD754) is a deoxycytidine analogue nucleoside reverse transcriptase inhibitor in clinical development for patients with HIV disease. This study evaluated the antiretroviral efficacy, tolerability and safety of apricitabine monotherapy, administered for 10 days in antiretroviral-naive, HIV-1 infected adults. Adult patients (> or = 18 years) with HIV infection (CD4 count > or = 250 cells/microl; plasma HIV-1 RNA level 5000-100 000 copies/ml) were randomized to 10 days' double-blind oral therapy with placebo or apricitabine 400 mg/day, 800 mg/day, 1200 mg/day, or 1600 mg/day. At 7 days, all apricitabine doses produced statistically significant log10
Multiple-dose pharmacokinetics of apricitabine, a novel nucleoside reverse transcriptase inhibitor, in patients with HIV-1 infection. This study aimed to investigate the multiple-dose pharmacokinetics of apricitabine, a novel deoxycytidine analogue reverse transcriptase inhibitor, in antiretroviral-naive patients with HIV-1 infection. This was an international, randomized, double-blind, placebo -controlled, multicentre, dose-ranging study. Patients received 10 days' oral placebo or apricitabine 200, 400, 600 or 800 mg twice daily or 800 or 1200 mg once daily. On days 1 and 8, blood and urine samples were collected over 24 hours for pharmacokinetic analysis. Apricitabine triphosphate pharmacokinetics were investigated in peripheral blood mononuclear cells (PBMCs) on day 8. Overall, 63 patients
Comparison of the pharmacokinetics of apricitabine in the presence and absence of ritonavir-boosted tipranavir: a phase I, open-label, controlled, single-centre study. Apricitabine is a deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of HIV infection. The aim of this phase I study was to investigate whether administration of apricitabine with the HIV protease inhibitor tipranavir (ritonavir-boosted) affects the pharmacokinetic profile of apricitabine. This phase I study was conducted in 18 healthy adult male subjects. Subjects received a single dose of apricitabine 800 mg on the morning of day 1 followed by tipranavir 500 mg plus ritonavir 200 mg every 12 hours from day 2 to day 9 to achieve steady-state concentrations of tipranavir/ritonavir. On day 10
Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy. Apricitabine (ATC) is a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor (NRTI) with significant antiviral activity in vitro, including activity against HIV-1 with reverse transcriptase mutations that confer resistance to other NRTIs. ATC has
In vitro interactions between apricitabine and other deoxycytidine analogues. Apricitabine is a novel deoxycytidine analogue reverse transcriptase inhibitor that is under development for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Apricitabine is phosphorylated to its active triphosphate by deoxycytidine kinase, which is also responsible for the intracellular phosphorylation of lamivudine (3TC) and emtricitabine (FTC); hence, in vitro studies were performed to investigate possible interactions between apricitabine and these agents. Human peripheral blood mononuclear cells (PBMC) were incubated for 24 h with various concentrations of (3)H-labeled or unlabeled apricitabine, 3TC, or FTC. Intracellular concentrations of parent compounds and their phosphorylated
transcriptase inhibitors (NRTIs) beta-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (Reverset), beta-D-5-fluorodioxolane-cytosine, and apricitabine. As controls, viruses from NRTI-naïve patients were also studied. The pol RT region (codons 21 to 250) of the viruses were sequenced and evaluated for mutations in the RNase H domain (codons 441 to 560) and the connection domain (codons 289 to 400). The results
A Study to Investigate the Cardiovascular Safety of Apricitabine in Healthy Subjects A Study to Investigate the Cardiovascular Safety of Apricitabine in Healthy Subjects - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers: refer to the Data Element Definitions if submitting studies (100).Please remove one or more studies before adding more. A Study to Investigate the Cardiovascular Safety of Apricitabine in Healthy Subjects The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov
Pharmacokinetics of Apricitabine and Tipranavir When Dosed Alone or Together Pharmacokinetics of Apricitabine and Tipranavir When Dosed Alone or Together - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers: refer to the Data Element Definitions if submitting registration studies (100).Please remove one or more studies before adding more. Pharmacokinetics of Apricitabine and Tipranavir When Dosed Alone or Together The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov
A Long Term, Safety Study of Apricitabine in HIV-infected Subjects A Long Term, Safety Study of Apricitabine in HIV-infected Subjects - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers: refer to the Data Element Definitions if submitting registration or results information ).Please remove one or more studies before adding more. A Long Term, Safety Study of Apricitabine in HIV-infected Subjects The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT00367952
A Long Term Safety Study of Apricitabine in HIV-infected Patients A Long Term Safety Study of Apricitabine in HIV-infected Patients - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers: refer to the Data Element Definitions if submitting registration or results information ).Please remove one or more studies before adding more. A Long Term Safety Study of Apricitabine in HIV-infected Patients The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT00686270
Study of the Efficacy and Safety of Apricitabine, a New NRTI, to Treat Drug-resistant HIV Infection Study of the Efficacy and Safety of Apricitabine, a New NRTI, to Treat Drug-resistant HIV Infection - Full Text View - ClinicalTrials.gov Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort. Hide glossary GlossaryStudy record managers: refer to the Data WarningYou have reached the maximum number of saved studies (100).Please remove one or more studies before adding more. Study of the Efficacy and Safety of Apricitabine, a New NRTI, to Treat Drug-resistant HIV Infection The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal