Antivir Chem Chemother. 2007;18(6):343-6.

Short communication cellular pharmacology of 9-(beta-D-1,3-dioxolan-4-yl) guanine and its lack of drug interactions with zidovudine in primary human lymphocytes.

Hernandez-Santiago BI, Obikhod A, Fromentin E, Hurwitz SJ, Schinazi RF.

Source

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Veterans Affairs Medical Center, Decatur, GA 30033, USA.

Abstract

Amdoxovir, currently in Phase II clinical trials, is rapidly converted to 9-(beta-D-1,3-dioxolan-4-yl)guanine (DXG) by adenosine deaminase in vitro and in humans. The cellular pharmacology of DXG in primary human lymphocytes, including dose-response relationships, intracellular half-life of DXG triphosphate (DXG-TP), and combination studies were determined. DXG produced high levels of DXG-TP with a long half-life (16 h) in activated human peripheral blood mononuclear cells. Since zidovudine (ZDV) and DXG select for different resistance mutations, co-formulation of the these two drugs is an attractive proposition. A combination study between DXG and ZDV showed no reduction of DXG-TP or ZDV-TP. Taken together, these results suggest that an appropriately designed DXG prodrug could be given once a day and that co-formulation with ZDV might be a possibility.

PMID:: 18320938; [PubMed - indexed for MEDLINE]

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Short communication cellular pharmacology of 9-(beta-D-1,3-dioxolan-4-yl) guanine and its lack of drug interactions with zidovudine in primary human lymphocytes.

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