Antiviral effect in human cytomegalovirus-infected cells, pharmacokinetics, and intravitreal toxicology in rabbits of acyclovir diphosphate dimyristoylglycerol.
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.
Shakiba
S
S
Department of Ophthalmology, University of California, San Diego, La Jolla 92093, USA.
Freeman
W R
WR
Flores-Aguilar
M
M
Munguia
D
D
Tatebayashi
M
M
Besen
G
G
Amani
R
R
Wiley
C A
CA
Vuong
C
C
Aldern
K A
KA
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*
D000998:Antiviral Agents; D004337:Drug Carriers; D008081:Liposomes; D010715:Phosphatidylglycerols; D011355:Prodrugs; C084886:acyclovir diphosphate dimyristoylglycerol; D015774:Ganciclovir; D000212:Acyclovir