Isobolographic analysis of propofol-thiopental hypnotic interaction in surgical patients

Drugs acting via the same mechanism, interact additively, whereas a supraad ditive effect can result from an interaction of drugs with different mechan isms of action. Hypnotic midazolam-propofol and midazolam-thiopental intera ctions are supraadditive, In contrast to midazolam, the mechanisms of actio ns of propofol and thiopental are quite similar. The aim of this study was to test the hypothesis that similarity in the mechanisms of action of propo fol and thiopental results in the additive hypnotic interaction. We studied the hypnotic effects of thiopental, propofol, and their combinations in 15 0 unpremedicated patients in a randomized, double-blind fashion. The abilit y to open eyes on command was used as an end point. Dose-response curves fo r the drugs given separately and in combinations at three different dose ra tios between the drugs were determined by using a probit procedure, and the 50% effective dose values were compared by using isobolographic and algebr aic (fractional) analysis. The hypnotic propofol-thiopental combination was additive with all dose ratios between components of the combination. The a bsence of propofol-thiopental synergy, as demonstrated with midazolam-thiop ental or propofolmidazolam combinations, suggests that the mechanisms under lying the hypnotic effects of propofol and thiopental, in contrast to the a bove combinations with midazolam, are very similar and could be identical. Implications: The propofol-thiopental hypnotic interaction is additive.