1. What is the purpose of pre-clinical evaluation in drug development? Explain the main

phases and types of studies involved.

- The purpose of pre-clinical evaluation is to assess the safety, efficacy, pharmacokinetics

and pharmacodynamics of a new drug candidate before testing it in humans. The main

phases are discovery, lead optimization, preclinical development and IND-enabling

studies. The types of studies include in vitro assays, in vivo animal models,

toxicology, pharmacology, ADME and bioanalysis.

2. What are the advantages and limitations of using animal models in pre-clinical

evaluation? Give examples of some commonly used animal species and their

relevance to human diseases.

- The advantages of using animal models are that they can mimic some aspects of human

physiology and pathology, provide insights into the mechanisms of action and

potential side effects of a drug, and allow for ethical and practical testing of different

doses and routes of administration. The limitations are that they may not fully reflect

the human response to a drug, have different metabolic and immune systems, and pose

ethical and logistical challenges. Some commonly used animal species are mice, rats,

rabbits, dogs, monkeys and pigs. They are relevant to human diseases such as cancer,

diabetes, cardiovascular diseases, infectious diseases and neurological disorders.

3. What are the main ethical principles and guidelines that govern the conduct of pre-

clinical evaluation? Name some national and international organizations that oversee

the regulation and oversight of pre-clinical research.

- The main ethical principles and guidelines are the 3Rs: replacement, reduction and

refinement. Replacement means using alternative methods that do not involve animals

whenever possible. Reduction means using the minimum number of animals necessary

to achieve the scientific objectives. Refinement means minimizing the pain, distress

and suffering of animals and enhancing their welfare. Some national and international

organizations that regulate and oversee pre-clinical research are the FDA, EMA, ICH,

OECD, AAALAC and NRC.

4. What are some methods and techniques used to measure the pharmacokinetics and

pharmacodynamics of a drug in pre-clinical evaluation? Define the terms

bioavailability, clearance, volume of distribution, half-life, Cmax, Tmax, AUC and

bioequivalence.

- Some methods and techniques used to measure the pharmacokinetics and