Section 7
Chapter 6,796

Therapeutic activities of 1 2 fluoro 2 deoxy beta d arabinofuranosyl 5 iodo cytosine and 1 2 fluoro 2 deoxy beta d arabinofuranosyl 5 iodo thymine alone and in combination with acyclovir and vidarabine in mice infected intra cerebrally with herpes simplex virus

Schinazi, R.F.; Peters, J.; Sokol, M.K.; Nahmias, A.J.

Antimicrobial Agents and Chemotherapy 24(1): 95-103


ISSN/ISBN: 0066-4804
Accession: 006795570

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The therapeutic effectiveness of 2 new antiviral agents, 1-(2-fluoro-2-deoxy-.beta.-D-arabinofuranosyl)-5-iodocytosine and 1-(2-fluoro-2-deoxy-.beta.-D-arabinofuranosyl)thymine, was compared with that of acyclovir and vidarabine. In mice inoculated intracerebrally with high LD50 of herpes simplex virus type 2, nontoxic i.p. or oral treatments with the 2 new fluorinated antiviral agents were highly effective in reducing mortality. The 2 drugs were also effective when treatment has begun as late as 48 h after virus inoculation. The relative order of potencies of the drugs when compared on a molar basis or in terms of therapeutic index was 1-(2-fluoro-2-deoxy-.beta.-D-arabinofuranosyl)thymine >> 1-(2-fluoro-2-deoxy-.beta.-D-arabinofuranosyl)-5-iodocytosine > vidarabine .simeq. acyclovir. The new pyrimidine analogs lacked immunosuppressive activity in mice. The combination of 1-(2-fluoro-2-deoxy-.beta.-D-arabinofuranosyl)-5-iodocytosine and vidarabine was the most effective; significantly greater reduction in mortality was achieved with this combination than with either drug alone. Thirty minutes after i.p. treatment with the fluorinated analogs, the drugs (or their metabolites) were transported to the brains of virus-inoculated and normal mice at levels .apprx. 1/3-2/3 those in the blood. The levels of 1-(2-fluoro-2-deoxy-.beta.-D-arabinofuranosyl)thymine in the blood or brain were consistently higher than those found with equivalent i.p. doses of the 5-iodocytosine analog.

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