Maximum tolerable dose (MTD) studies

Maximum tolerable dose (MTD) studies define the highest dose of a drug or therapy that does not cause unacceptable side effects or toxicity. These studies help determine safe starting doses for first in-human (FIH) clinical trials and may continue during the development of a clinically viable therapy. Data from these studies can be used to avoid conventional single dose toxicology studies.

The MTD can be determined by acute toxicity studies, short duration dose escalation studies and dose ranging studies. The MTD study is followed by the dose range-finding and definitive anti-tumor efficacy studies. Generally, tolerance is assessed by clinical observations, body weight and macroscopic observations at euthanization.

MTD studies are often conducted prior to in vivo pharmacokinetic (PK) and ADME studies; however, depending on the study, other methods of determining dosage may be more appropriate, e.g., maximum feasible dose (MFD), exposure saturation, limit dose (1000 mg/kg) and dose providing a 50-fold margin of exposure.

These studies are also performed when producing an agricultural/crop protection product or when analyzing chemical compounds.