Inhibitory effect of FK-565 alone and in combination with zidovudine on retroviral infection by Friend leukemia virus in mice.
The effects of route and starting time of administration on FK-565 inhibition of splenomegaly by Friend leukemia virus (FLV) were studied in mice, and the concomitant effect of FK-565 in allowing reduction of zidovudine dosage was estimated. FK-565 inhibited splenomegaly in intravenous and oral doses of 0.01 to 1 mg/kg, but time of initial dosing had little effect on this inhibition. When 0.01 or 1 mg/kg of FK-565 was given intravenously with intraperitoneal doses of 0.63, 2.5, 10 and 40m g/kg of zidovudine, the inhibition rate of splenomegaly at all doses was markedly and dose-dependently higher than when either drug was given alone, and the concomitant use of FK-565 with zidovudine enabled a 16-fold reduction of the dose of zidovudine. The survival rate and survival time after infection with massive amounts of FLV were higher when FK-565 1 mg/kg and zidovudine 20 mg/kg were given in combination than when either drug was given alone. Inhibition of FLV splenomegaly was reflected in the prolonged survival time of the infected mice.
Yokota
Y
Y
Product Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Wakai
Y
Y
Watanabe
Y
Y
Mine
Y
Y
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005622:Friend murine leukemia virus / Q000187:drug effects*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
D009842:Oligopeptides; D015215:Zidovudine; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine