Maximum Tolerated Dose (MTD) Services

Drug discovery and drug development involves many disciplines. Promising compounds are screened for favorable biological activity against a target and are moved forward to be evaluated for toxicity and ADME properties.

An important part of preclinical drug development is to define the dose and schedule for Phase I clinical trials (First In Man).

Before conducting in vivo PK and ADME studies to determine the dosing schedule, the dose has to be defined. There are typically five options for defining a dose: Maximum Tolerated Dose (MTD), Maximum Feasible Dose (MFD), limit dose (1000mg/kg), exposure saturation, and dose providing a 50-fold margin of exposure. The most common of these, the maximum tolerated dose, is defined as the highest dose of a drug that does not cause unacceptable side effects or overt toxicity in a specific period of time. The MTD can be determined by acute toxicity studies, short duration dose escalation studies and dose ranging studies. These studies are designed with a minimum number of animals and include toxicological endpoints such as clinical observations and clinical pathology, for example blood tests for liver function. This maximum tolerated dose is then used for longer-term safety assessments. The rationale for using the MTD in long term studies is to maximize the likelihood of detecting any chronic disease effects or other hazards of a drug candidate.