Comparative activity of penciclovir and acyclovir in mice infected intraperitoneally with herpes simplex virus type 1 SC16.
Penciclovir [PCV; 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] is a potent and selective inhibitor of herpes simplex virus and varicella-zoster virus in human cell culture. We have compared the activities of PCV and acyclovir (ACV) in DBA/2 mice infected intraperitoneally with herpes simplex virus type 1 SC16 by measuring the amount of virus in peritoneal washings. In untreated mice after an eclipse phase, virus titers are maximum at 48 h after infection and decline thereafter. PCV and ACV reduced virus replication to a similar extent when given ad libitum in drinking water, even though ACV had better oral bioavailability and greater potency in murine cells. Thus, PCV was more active than had been predicted. In dose-response experiments, PCV given as a single subcutaneous dose 24 h after infection was active at a 10-fold-lower dose than ACV (P < 0.01). A single subcutaneous dose of PCV at 5 h after infection prevented virus replication for 3 days and was more effective than three doses of ACV given 1, 5, and 20 h after infection (P < 0.05). The superior activity of PCV following discrete dosing is not due to pharmacokinetic differences but is probably a reflection of the known stability of the intracellular triphosphate. In this model, the maintenance of high concentrations in blood is less important for PCV than for ACV and may lead to less-frequent doses in clinical use.
SmithKline Beecham Pharmaceuticals, Epsom, Surrey, United Kingdom.
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D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005260:Female; D006147:Guanine; D006561:Herpes Simplex / Q000188:drug therapy* / Q000382:microbiology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018139:Simplexvirus; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C053539:penciclovir; D006147:Guanine; D000212:Acyclovir