deoxy-guanosine triphosphate (dGTP)
FIGURE 49-2 Conversion of acyclovir to acyclovir triphosphate leading to DNA chain termination. Acyclovir is converted to the monophosphate (MP) derivative by a herpes virus thymidine kinase. Acyclovir-MP is then phosphory-lated to acyclovir-DP and acyclovir-TP by cellular enzymes. Uninfected cells convert very little or no drug to the phos-phorylated derivatives. Thus, acyclovir is selectively activated in cells infected with herpesviruses that code for appropriate thymidine kinases. Incorporation of acyclovir-MP from acyclovir-TP into the primer strand during viral DNA replication leads to chain termination and formation of an inactive complex with the viral DNA polymerase. (Adapted from Elion, 1982, with permission.)
Acyclovir distributes widely in body fluids, including vesicular fluid, aqueous humor, and cerebrospinal fluid (CSF). Compared with plasma, salivary concentrations are low, and vaginal secretion concentrations vary widely. Acyclovir is concentrated in breast milk, amniotic fluid, and placenta. Newborn plasma levels are similar to maternal ones. Percutaneous absorption of acy-clovir after topical administration is low.
The plasma elimination half-life of acyclovir is ~2.5 hours in adults with normal renal function, 4 hours in neonates, and 20 hours in anuric patients. Renal excretion of unmetabolized acy-clovir by glomerular filtration and tubular secretion is the principal route of elimination.
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