Therapy of coxsackie virus B3-induced myocarditis with WIN 54954 in different formulations.
The antiviral efficacy of WIN 54954 was demonstrated in vivo in a Coxsackie B 3 virus (Woodruff strain) induced myocarditis mouse model. The model was selected because of the high mortality rate during the first week, which was convenient for antiviral therapy regimen studies. The antiviral component WIN 54954 was found to inhibit the early virus-induced mortality almost completely if treatment was started at the same time as virus was inoculated. However, there was still a late mortality, occurring at 1-2 months after virus inoculation. Non-infected mice which were treated with the drug did not show any such late effects. However, drug treatment in non-infected mice did not cause any mortality. When therapy was delayed for one day, 85% survived for 3 weeks as compared to 100% mortality after just over 3 weeks in the infected control group (p < 0.05). With a delay of 4 days after viral inoculation, a therapeutic effect was still noted. Thus, mortality was virtually abrogated when the compound was given early, but the effect vanished with time of delay. Different preparations of the WIN 54954 substance were tried, and it was found that a fat emulsion containing several nutrients (Nutrodrip) was superior to other used formulations. We conclude that the use of the antiviral drug WIN 54954 in treatment of enteroviral associated diseases is of great value if therapy is started early. Thus therapy is almost fully effective within 24 hours of infection, but the beneficial effects decline with time. Nutrodrip oil emulsion was found superior as vehicle as compared to other formulations.(ABSTRACT TRUNCATED AT 250 WORDS)
Dept Infectious Diseases, University Hospital, Uppsala, Sweden.
K
K
Pauksen
N G
NG
Ilbäck
G
G
Friman
J
J
Fohlman
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000473:pathology; D004304:Dosage Forms; D029822:Enterovirus B, Human / Q000187:drug effects*; D005260:Female; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D014677:Pharmaceutical Vehicles
D000998:Antiviral Agents; D004304:Dosage Forms; D007555:Isoxazoles; D014677:Pharmaceutical Vehicles; C062554:Win 54954