[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.
Isobe
Y
Y
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
D000818:Animals; D003114:Colony-Forming Units Assay; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay
D005472:Fluorouracil