A model for mimicking the pharmacokinetics of chemotherapy drugs for evaluation of drug effects in a soft agar colony formation assay system.

Abstract

Colony formation assay systems are an important part of in vitro drug evaluation. It would be useful if the in vitro drug cytotoxicity could be carried out under conditions mimicking those employed clinically. We have developed an individual colony formation assay system that would allow monitoring and quantitation of the growth of individual colonies (9) in the presence of the drug under conditions of continuous and/or short-term exposure, after plating of the cells in the agarose. In this brief report, we established the pharmacokinetic profile of four drugs, cytosine arabinoside (araC), Doxorubicin (Dox), 5-fluorouracil (5-FUra) and 5-fluoro-2'-deoxyuridine (FdUrd) in agarose mimicking those that are achieved when these agents were administered in vivo as an i.v. push. The results show that short-term treatment in agarose is possible and that the washing procedure of the drugs decreased the drug concentrations 3-4 logs over 44 hours.