it is a viral DNA polymerase inhibitor but does not readily block the polymerase of the
host cell. Therefore, acyclovir is a spectacularly nontoxic drug [LD 50 (mouse)= 1000
mg/kg, i.p.] and is not degraded metabolically. Valacyclovir (9.10) is the L-valyl ester
of acyclovir. After oral administration valacyclovir is rapidly converted to acyclovir,
attaining serum concentrations 3–5 times higher than those achieved with oral acyclovir.
Valacyclovir has been successfully used in doses of 2 grams four times daily.
Famciclovir (9.11) is the diacetyl ester prodrug of 6-deoxy penciclovir (9.12), an
acyclic guanosine analog; in doses of 500 mg every 12 hours, famciclovir is an effec-
tive viral DNA polymerase inhibitor. Ganciclovir (9.13) is an acyclic guanosine analog
that requires triphosphorylation prior to being activated as a viral DNA polymerase
inhibitor. Cidofovir (9.14) is a cytosine nucleotide analog with activity against HSV-1,
HSV-2, adenovirus, and poxvirus.
Another anti-herpes compound is the remarkably simple foscarnet (9.15, phospho-
noformate). This is an inorganic pyrophosphate compound that inhibits viral DNA
polymerase and RNA polymerase without requiring activation by phosphorylation.
Fomivirsen is an oligonucleotide that inhibits human cytomegalovirus (CMV) via an
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