The Importance of Maximum Tolerated Dose (MTD) Testing in Preclinical Research

Maximum tolerated dose (MTD) is defined as the maximum dose of a drug or therapy that can be administered for a specified period of time without causing unacceptable side effects or toxicity. MTD studies help define safe starting doses for first-in-human (FIH) clinical trials and may continue during the development of clinically viable therapies. MTD studies are performed before in vivo pharmacokinetic (PK) and ADME studies. However, depending on the study, other methods of determining dose may be more appropriate, such as maximum feasible dose (MFD), exposure saturation, limiting dose (1000 mg/kg), and doses that provide a 50-fold exposure margin. One of the first steps in any drug development program should be MTD testing. It aims to find a range of doses showing signs of toxicity that are considered to be the highest doses that can be tolerated with prolonged dosing. The MTD was determined through acute toxicity studies, short-term dose escalation studies, and dose-ranging studies. These studies use a minimal number of test species and include toxicological endpoints such as clinical observations, body weight changes, and clinical pathology to determine potential acute toxicity.

Service Overview

Ace Therapeutics is a comprehensive preclinical ophthalmic research CRO. We provide a wide range of ocular toxicology studies, such as single-dose toxicity studies and repeated-dose chronic toxicity studies, to determine the MTD after short-term exposure through the expected clinical trials to meet your pivotal study or IND enabling study.

At Ace Therapeutics, our toxicology team has the knowledge and experience to help our clients determine the MTD for single and multiple doses of their novel ophthalmic compounds.

What Problems Can We Solve?

Ace Therapeutics conducts preliminary in vivo toxicity studies to determine the appropriate dose, frequency, and route of administration. During ocular tolerability assessments, compounds are first evaluated in a single dose escalation phase, in which the test system receives single doses expected to achieve relevant multiples of the efficacious dose. Data from this phase assess absorption and are useful for estimating the maximum tolerated dose for a single dose and for determining doses for the repeat dosing phase. Interestingly, whether single-dose or multiple-dose may induce dose-limiting signs of toxicity and allow the selection of dose levels for regulatory studies.

Overall, our toxicology research team will design flexible study protocols based on the properties of your compound to define doses that can be used for future studies.

Ace Therapeutics' MTD study of ophthalmic compounds is to assign models (canine, mini-pig, mouse, rabbit, rat, etc.) to different treatment groups and expose them to different graded dose levels to determine the toxicity of each dose level and determine the MTD.

• Clinical endpoint
  Mortality (at least twice daily).
  Clinical symptoms of toxicity (routine/detailed).
  The measurement of body weight and food consumption.
  Gross pathology.
  Terminal clinicopathology.
  Limited histopathology.

Ace Therapeutics is pleased to provide the MTD study of ophthalmic compounds services to help you select appropriate doses. If you are interested in our services or need more detailed information, please feel free to contact us. Our experienced scientists are ready to help you!

Reference

1. Zhang Q, Zeng SX, Lu H. Determination of Maximum Tolerated Dose and Toxicity of Inauhzin in Mice. Toxicol Rep. 2015;2:546-554.

• Acute Local Toxicity Testing of Ophthalmic Drugs
• Chronic Local Toxicity Testing of Ophthalmic Drugs
• Lacrimation Testing of Ophthalmic Drugs
• Corneal Anesthesia Testing of Ophthalmic Drugs
• Pupil Diameter Testing of Ophthalmic Drugs

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