Communicating synergism in drug combination studies.
Isobolograms are used to identify synergistic effects of drugs given in combination. However, the traditional isobologram provides only a qualitative determination of synergism. The present report describes two procedures for quantifying the synergistic actions of drugs based on isobolographic plots. The point at which the derivative of the isobolar curve equals negative one provided an estimate of the optimal dose ratio and the axis intercept of the tangent to the curve at this point provided an estimate of the extent of expected dose synergism. The degree of effect potentiation was expressed by calculating the ratio of the observed to that expected if the drugs were simply additive in their effects. These procedures provide two direct, although non-statistical, means to communicate synergism in drug combination studies.
Brodkin
J
J
Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana, USA. Jesse_Brodkin@merck.com
Shannon
H E
HE
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D007052:Ibuprofen / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008962:Models, Theoretical; D013830:Thiadiazoles / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D004338:Drug Combinations; D013830:Thiadiazoles; C101714:LY 297802; D007052:Ibuprofen