Analysis of the rocuronium-vecuronium interaction on tetanic fade based on a generalized response surface model with varying relative potencies

Lee, Jong Hwan; Lee, Soo Il; Lee, Seung Cheol; Cho, Won Joon

Abstract

BACKGROUND: Some studies have shown that rocuronium and vecuronium have additive, or synergistic effects on muscle relaxation based on the Loewe additivity. Therefore, we performed a fit of tetanic fade data to a generalized response surface model with varying relative potencies proposed by Kong and Lee (KLGRS) to evaluate the usefulness of KLGRS for capturing the interspersed drug interactions and to characterize the interaction between the two drugs.
METHODS
Left phrenic nerve-hemidiaphragms (Male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Supramaximal electrical stimulation (0.2 ms, rectangular) of 50 Hz for 1.9 s to the phrenic nerve evoked tetanic contractions that were measured with a force transducer. Each preparation was exposed to one of 4 vecuronium concentrations (0.0, 1.5, 2.5, and 3.0 microM), or one of 4 rocuronium concentrations (0.0, 3.0, 4.5, and 5.5 microM). Subsequently the adequate amount of rocuronium was added to a vecuronium bath and that of vecuronium was added to a rocuronium until an 80-90% increase in tetanic fade was achieved. We then fitted the modified KLGRS models to the above data, after which we selected the best model, based on 5 methods for determining goodness of fit. Using this method, we obtained the response surface, as well as contour plots for the response surface (i.e. isoboles), the polynomial function and the interaction index.
RESULTS
The model with the constant relative potency ratio and 8 parameters was found to best describe the results, and this model reflected well the characteristics of the raw data. In addition, the two drugs showed a synergistic interaction in almost every area and an antagonistic one in a very narrow area.
CONCLUSIONS
KLGRS was found to be a useful method of analyzing data describing interspersed drug interactions. The interaction between rocuronium and vecuronium was found to be synergistic.