Maximum tolerated dose MTD

For most pharmaceutical companies, the doses selected are as follows. The highest dose is selected to be the estimated maximum tolerated dose (MTD). The lowest dose is usually a small multiple (1 to 5 times) of the MRHD, and the middose approximates the geometric mean of the other two doses (PMA, 1988 McGregor, 2000). 

In the development of cytotoxic drugs in oncology, dose-finding usually means establishing a maximum tolerated dose (MTD). This is the dose associated with serious but reversible side effects in a sizable proportion of patients and the one that... 

Nevertheless, this study had several limitations. Initial doses were not well tolerated because of exceedence of the Maximum Tolerated Dose (MTD) as indicated by excessive deaths. Doses were reduced 17-33% from initial doses once or twice during the experiment. During the final 75 days of treatment, high dose males received chlordecone on alternative weeks only. Doses above the MTD were used for 42-386 days. An unusually high mortality rate occurred in control animals also, and only pooled controls were used in this bioassay. 

The N-hydroxyethyl analogue NVP-LAQ824 (Table 2, Fig. 17) also showed good overall potency in vitro, but excelled in the succeeding in vivo experiments. It demonstrated the highest maximum tolerated dose (MTD ... 

Figure 17.7 Predicted versus observed human in vivo MTD using colony forming unit (CPU) assay.ThemouseCFU-CM IC50, humanCFU-GM ICsoand mouse maximum tolerated dose (MTD) were used to calculate predicted human MTD...

Croera, C., Gagliardi, G., Foti, R., Parchment, R., Parent-Massin, D., Schoeters, G., Sibiril, Y, Van Den Heuvel, R. and Grialdo, L. (2003) Application of the CFU-GM assay to predict acute drug-induced neturopenia an interanational blind trial to validate a prediction model of the maximum tolerated dose (MTD) of myelosuppresive xenobiotics. Toxicol Sciences, 75, 355-367. 

McLaughlin, J.E.. Pamo, J., Gamer, F.M., Clary, J.J., Thomas, W.C. Murphy, S.R. (1995) Comparison of the maximum tolerated dose (MTD) dermal response in three strains of mice following repeated exposure to acrylic acid. Food chem. Toxicol., 33, 507-513... 

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