J.Jpn. Surg. Soc.. 89(10): 1594-1602, 1988
Original article
PHARMACODYNAMIC STUDY OF THE IN VITRO CLONOGENIC ASSAY
－WITH REFERENCE TO THE DOSE LEVELS－
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Department of Surgery, School of Medicine, Keio University, Tokyo, Japan Yoh Isobe |
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 3μg/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.
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