Abstract
Acyclovir diphosphate dimyristoylglycerol (ACVDP-DG) is a lipid prodrug which is active against ACV-resistant strains of herpes simplex virus because of its intracellular metabolism to ACV monophosphate. In human cytomegalovirus (HCMV)-infected MRC-5 cells, ACVDP-DG was ninefold more active than ACV. When liposomal [8-3H]ACVDP-DG was injected intravitreally at the maximum nontoxic dose of 1 mumol in rabbits, the drug remained above its estimated 90% HCMV-inhibitory concentration for 18 days. Intravitreal ganciclovir persists above its 90% inhibitory concentration for only 1 to 2 days. ACVDP-DG may be useful as a local treatment for HCMV retinitis.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acyclovir / analogs & derivatives*
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Acyclovir / pharmacokinetics
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Acyclovir / pharmacology
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Acyclovir / toxicity
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Animals
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Antiviral Agents / pharmacokinetics
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Antiviral Agents / pharmacology*
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Antiviral Agents / toxicity
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Cells, Cultured
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Cytomegalovirus / drug effects
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Drug Carriers
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Ganciclovir / pharmacokinetics
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Humans
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Liposomes
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Phosphatidylglycerols / pharmacokinetics
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Phosphatidylglycerols / pharmacology*
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Phosphatidylglycerols / toxicity
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Prodrugs / pharmacokinetics
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Prodrugs / pharmacology*
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Prodrugs / toxicity
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Rabbits
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Virus Replication / drug effects
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Vitreous Body / metabolism*
Substances
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Antiviral Agents
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Drug Carriers
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Liposomes
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Phosphatidylglycerols
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Prodrugs
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acyclovir diphosphate dimyristoylglycerol
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Ganciclovir
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Acyclovir