Apricitabine: a nucleoside reverse transcriptase inhibitor for HIV infection.

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Gaffney MM, Belliveau PP, Spooner LM

Apricitabine: a nucleoside reverse transcriptase inhibitor for HIV infection.

Ann Pharmacother. 2009 Oct;43(10):1676-83. doi: 10.1345/aph.1M160. Epub 2009 Sep 8.

PubMed ID

19737995 [ View in PubMed

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Abstract

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of apricitabine, a nucleoside reverse transcriptase inhibitor that is currently under investigation and has fast-track approval status with the Food and Drug Administration. DATA SOURCES: A literature search was conducted using PubMed (1966-June 2009) to retrieve relevant material using the search terms apricitabine, SPD754, and AVX754. References from selected articles were evaluated to identify other pertinent trials. Information was also obtained from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: All English-language in vitro and in vivo studies and abstracts evaluating apricitabine were reviewed and considered for inclusion. Preference was given to human data. DATA SYNTHESIS: Apricitabine is a prodrug that is phosphorylated to its active triphosphate form intracellularly, which ultimately results in chain termination and inhibition of reverse transcription. Apricitabine is administered orally, displays linear pharmacokinetics, and is renally excreted with minimal to no hepatic metabolism. It has demonstrated antiretroviral activity against drug-resistant strains both in vitro and in vivo. In clinical studies, in both antiretroviral-naive and treatment-experienced patients, apricitabine achieved the primary endpoint of significant reductions in plasma viral load versus comparator. Further Phase 2 and 3 studies are currently enrolling. Safety analysis indicates that apricitabine is well tolerated and has a low potential for causing mitochondrial damage. The most common adverse events reported include headache and rhinitis. Development of resistance or further gene mutations has not been shown in clinical studies to date. CONCLUSIONS: Although the role of apricitabine in the treatment of HIV-1 infection has yet to be established, its activity against resistant HIV-1 strains and its tolerability profile will likely make it a viable second-line treatment option in patients who have failed regimens containing lamivudine or emtricitabine.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Apricitabine	Reverse transcriptase/RNaseH	Protein	Human immunodeficiency virus 1	Unknown	Inhibitor	Details