Dose Range Finding (DRF) is a scientific approach to determine the appropriate dose of a product to administer in preclinical trials. Generally, DRF studies are initially carried out in rodents, progressing to non-rodents when the adverse effects are understood.

Dose selection of the first regulatory studies, typically up to one month, are usually based on DRF studies of 7-14 days. The toxic effect of the test items and the Maximum Tolerated Dose (MTD) should be determined in the initial DRF studies when small numbers of animals are exposed to the highest severity of effects.

DRF studies may be divided into two phases:

• A dose escalation phase consisting of a single or small number of repeated administrations to establish MTD for short-term duration
• A fixed dose repeat dose typically of 7-14 days duration. The goal is to establish potential organ toxicity and tolerability by monitoring clinical signs
   

How is it done?

The main objective of regulatory toxicology studies is to establish the potential hazards associated with the test item by identifying potential organ toxicity. Determining an appropriate dose requires relevant experience and judgement as it is often influenced by the nature of the test item, its targeted pharmacology and its intended therapeutic use in humans.

The primary parameter used in dose selection is the tolerability of the test dose in animals. Tolerability can be determined by:

• Observations such as clinical signs, reduction in body weight or a decrease in food consumption 
• Systemic exposure measured at the concentration of the test item, bound and unbound, in plasma/serum or blood
• Histopathology is used to support dose selection
• Depending on the test item, other parameters may be required, i.e. changes in haematology parameters of anti-cancer drugs, or blood pressure/ECG effects for compounds targeting the cardiovascular system