Determinaton of the Maximum Tolerated Dose
The identification of the Maximum-Tolerated Dose (MTD) is one of the first steps when taking a drug candidate from in vitro to in vivo phase of drug discovery. The MTD is the dose at which a certain degree of toxicity specified in advance occurs only in a pre-determined tolerable proportion of the animals.
The frequency and the route of administration play a role in the MTD as well as the mouse strain and the sex. When determining a maximum tolerable dose, the highest dose that promises the best antitumor effectiveness should be determined according to the motto "the more, the better" (proven for cytostatics), but does not trigger any severe side effects or death.
MTD studies can be performed in tumor-bearing mice since tumor exposure can have an impact on how a mouse tolerates a drug.