Use of alternative dose schedules for the determination of sublethal doses of potential antiviral drugs in mice.
In mice the ratio between maximally tolerated sublethal doses (MTD) after single and repeated administration of benzoxazolyl-2-formyl-S-ethyl-isothiosemicarbazone (ZIMET 111/74) was found to be different after s.c., p.o. or i.p. administration. Comparing the treatment schedules with relatively high or low initial doses, no differences of the total MTD were found. Using MTD after single drug administration (MTDs) as initial doses for repeated administration, the subsequent doses had to be reduced in a different manner for s.c. and p.o. administration to avoid lethality. As a result of these investigations a rule is proposed for compounds with similar mode of action and comparable pharmacokinetics to ZIMET 111/74 to calculate dose schedules for antiviral in vivo screening related to acute as well as to subacute toxicity data.
Amlacher
R
R
Central Institute of Microbiology and Experimental Therapy, Academy of Sciences of the GDR, Jena.
Hoffmann
H
H
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D051379:Mice; D008815:Mice, Inbred Strains; D013882:Thiosemicarbazones / Q000008:administration & dosage / Q000633:toxicity
D000998:Antiviral Agents; D013882:Thiosemicarbazones; C043258:Zimet 111-74