[Pharmacodynamic study of the in vitro clonogenic assay--with reference to dose levels]

To determine the optimal condition of the clonogenic assay, the antitumor activities of 5-fluorouracil (5-FU) in vitro and in vivo were investigated from a pharmacodynamic viewpoint using 8 human carcinoma xenografts. The clonogenic assay was performed by the continuous exposure method, and the antitumor effects were evaluated by the colony survival rates (T/Cs). The in vivo experimental chemotherapy was also performed by the nude mouse system, and the results were evaluated by the T/C ratios of the tumor weights. For pharmacokinetic analyses, the area under the concentration curves (AUCs) of 5-FU in vitro and in vivo were computed. The T/Cs of 5-FU were highly correlated to the AUCs both in vitro and in vivo. By using these AUC-T/C correlations, the concentration of 5-FU in the clonogenic assay to predict the T/C of the maximum tolerated dose in mouse was calculated to be 3 micrograms/ml mathematically. This concentration was then verified by the clonogenic assay, where T/Cs in vitro could successfully correspond to the T/Cs in vivo. (The predictable rate was 87.5%) From these results, this pharmacodynamic comparison between in vitro and in vivo chemosensitivities was thought to be a promising method for determining the conditions of the clonogenic assay.