title: Antiviral effect in human cytomegalovirus-infected cells, pharmacokinetics, and intravitreal toxicology in rabbits of acyclovir diphosphate dimyristoylglycerol.
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.
authors.affiliation: Department of Ophthalmology, University of California, San Diego, La Jolla 92093, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shakiba
authors.forename: W R
authors.initials: WR
authors.lastname: Freeman
authors.forename: M
authors.initials: M
authors.lastname: Flores-Aguilar
authors.forename: D
authors.initials: D
authors.lastname: Munguia
authors.forename: M
authors.initials: M
authors.lastname: Tatebayashi
authors.forename: G
authors.initials: G
authors.lastname: Besen
authors.forename: R
authors.initials: R
authors.lastname: Amani
authors.forename: C A
authors.initials: CA
authors.lastname: Wiley
authors.forename: C
authors.initials: C
authors.lastname: Vuong
authors.forename: K A
authors.initials: KA
authors.lastname: Aldern
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects; D004337:Drug Carriers; D015774:Ganciclovir / Q000493:pharmacokinetics; D006801:Humans; D008081:Liposomes; D010715:Phosphatidylglycerols / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D014779:Virus Replication / Q000187:drug effects; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D008081:Liposomes; D010715:Phosphatidylglycerols; D011355:Prodrugs; C084886:acyclovir diphosphate dimyristoylglycerol; D015774:Ganciclovir; D000212:Acyclovir