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Holzmann S et al.  
Dose-response curves of vasorelaxants: computerized calculation of combination effects using the example of nicorandil

Journal of Clinical and Basic Cardiology 1999; 2 (1): 96-98

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Fig. 1: Dosiswirkungsbeziehung - Nitroprussid Fig. 2: Dosiswirkungsbeziehung - Cromakalim

Keywords: additive Wirkungcomputergestützte BerechnungDosis-Wirkungs-BeziehungKombinationstherapieKonfidenzintervalleNicorandilcombinationscomputerized calculationconfidence intervalsdose-additivitydose-response curvesNicorandil

Aim of this study was to develop a convenient calculation of dose-response curves (DRCs) including those of theoretical model effects of combinations, using a commercial computer program which enables a clear visualization of confidence interval statistics and high quality graphs. The usefulness of this approach is exemplified by reevaluation of data from interaction experiments with nicorandil. Combination experiments were performed on bovine coronary artery strips in classical organ bath design. For the computerized calculation of DRCs, a ?program package? was developed for SigmaPlot, consisting of user-defined worksheet/graph and program files (curve fits and transforms). Visualization of statistical deviations of experimental from dose-additive = competitive interaction was achieved by showing bars of 95 % confidence intervals (CIs) and DRCs with CIs of dose-additive combinations. Non-overlapping CI-ranges were considered significantly different. Dual relaxant effects of nicorandil could be split into single components of action by using combination experiments. The comparison of experimental with theoretical model effects of combinations allows conclusions with respect to the molecular sites of drug action and gives an indication as to the mechanisms of vasorelaxant actions. J Clin Basic Cardiol 1999; 2: 96-8.
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