Some considerations in the experimental approach to distinguishing between membrane transport and intracellular disposition of antineoplastic agents, with specific reference to fluorodeoxyuridine, actinomycin D, and methotrexate
Analysis of the interaction between an anticancer agent and the intact cell can provide important clues to cytotoxic determinants and mechanisms of drug selectivity and resistance. This can be very useful in optimally evaluating single and multidrug regimens in test systems, designing new agents, and evaluating drug metabolism and binding to cellular target sites. This cellular pharmacokinetic approach requires very meticulous attention to experimental design, especially the time dimension chosen for study, and an appropriate framework for data analysis. This paper reviews cellular pharmacokinetic principles and experimental approaches that can be applied in uptake studies with cytotoxic agents, focusing, as examples, on studies from this laboratory with fluorodeoxyuridine, actinomycin D, and methotrexate.
- Research Organization:
- Department of Medicine, Medical College of Virginia, Richmond
- OSTI ID:
- 6377257
- Journal Information:
- Conn. Med.; (United States), Vol. 65 Suppl 3
- Country of Publication:
- United States
- Language:
- English
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