Preclinical Testing - Pharmacology and Pharmacokinetics

Question 1

What are the two primary types of studies in preclinical testing?

Answer 1

In Vitro Studies: Conducted on cells or tissues, assess toxicity and mechanisms of action.
In Vivo Studies: Animal studies for systemic effects and safety.

Question 2

What does specialized testing in preclinical studies involve?

Answer 2

Includes reproductive toxicity, genotoxicity, and carcinogenicity. Uses relevant animals or validated procedures to assess human risk.

Question 3

What are the key objectives of preclinical studies?

Answer 3

1. Assess toxicity on organ systems.
2. Determine safe starting dose for human trials.
3. Study pharmacokinetics and pharmacodynamics.
4. Fulfill regulatory requirements (MHRA, EMA, FDA).

Question 4

What are the stages of drug development?

Answer 4

1. Discovery and Development: Research to identify promising compounds.
2. Preclinical Research: Lab and animal testing for safety.
3. Clinical Research: Human trials for efficacy and safety.
4. Review: Regulatory body approval.
5. Post-Market Monitoring: Continuous safety assessment.

Question 5

What is GLP, and why is it important?

Answer 5

Definition: A set of rules and criteria for ensuring quality in non-clinical health and environmental safety studies.
Purpose: Ensures reliability and integrity of data for regulatory authorities.
Key Aspects: Study protocols, personnel qualifications, equipment, and reports.

Question 6

What is the purpose of ICH harmonization?

Answer 6

Define common standards across regions (e.g., US, UK, Japan). Reduce unnecessary animal testing. Encourage ethical and safe pharmaceutical development using new technologies.

Question 7

What are the key components of preclinical studies?

Answer 7

1. Pharmacology: Assess effects on vital functions (cardiovascular, respiratory, CNS).
2. Pharmacokinetics (ADME): Study absorption, distribution, metabolism, and excretion.
3. Toxicology: Investigate single/repeated dose toxicity and reproduction/genotoxicity.

Question 8

What are the key considerations for safety pharmacology studies?

Answer 8

Vital organs: Cardiovascular, respiratory, CNS.
Experimental design: Sample size, controls, route of administration, dose, and duration.
Metabolites: Evaluate parent compound and major metabolites.

Question 9

What are NOAEL and LD50?

Answer 9

NOAEL: Dose with no observable toxic effects.
LD50: Dose causing 50% mortality in a tested population (less commonly used now).

Question 10

What is the primary objective of toxicokinetics?

Answer 10

Describe systemic exposure and its relationship to dose and toxicity.

Question 11

What are the secondary objectives of toxicokinetics?

Answer 11

• Relate exposure to toxicological findings.
• Support species and treatment regimen selection.
• Design subsequent non-clinical studies.

Question 12

Which regulatory agencies oversee preclinical studies?

Answer 12

MHRA (UK), EMA (Europe), FDA (US).

Question 13

What are key challenges in preclinical studies?

Answer 13

• Differences in species responses (e.g., theobromine in dogs vs humans).
• Encouraging scientifically valid methods and new technologies.
• Proper experimental design to ensure valid conclusions.

Question 14

What is the role of preclinical studies?

Answer 14

• Bridge the gap between discovery and clinical trials.
• Ensure the safety and efficacy of drug candidates.
• Requires careful design, regulatory adherence, and ethical considerations.