Fig. 4

Lower concentrations of methotrexate synergize with the entire range of lovastatin concentrations tested. Shown are the single agent dose-response curves for lovastatin (a) and methotrexate (b). The experimental dose-response surface, (c), illustrates the efficacy of the dual-drug combinations and is overlain with synergy and antagonism according to the Loewe model. d. The Loewe synergy level matrix on day two (N = 4) indicates the statistically significant synergy populating the concentration space framed by the lower concentrations of methotrexate and nearly the entire concentration range of lovastatin. Significant antagonism is detected only with the highest two concentrations of methotrexate. e. On day three (N = 4), the overall pattern of interactions is similar to that on day two but antagonism is more pronounced. A detailed description of the various plots is given in Fig. 2