In certain polytherapy programs, ketoconazole can be administered with some antacids that could modify its dissolution rate and reduce its absorption leading to therapeutic failures. The aim of this work was to evaluate the influence of some excipients on this interaction in vitro. In this way, six formulations of directly compressible ketoconazole tablets were developed. The results confirmed that the dissolution rate of ketoconazole tablets was significantly reduced in the presence of antacids. Nevertheless this interaction was remarkably avoided in some of the formulations checked and in some conditions. In this way, the inclusion of a disintegrant (sodium starch glycolate) not only increased the dissolution rate of ketoconazole in the tablets, as expected, but it also modified the degree in which the dissolution rate was decreased in the presence of antacids. It was proved that a suitable selection of the excipients and therefore the modification in the rate in which the drug was released, could play an important role to modify a pharmacokinetic interaction based on a reduction of the solubility of the drug as a function of the pH value of the medium.