Drug Toxicity Studies

• Researchers use these studies to predict risks associated with a drug's use in human trials and real-world clinical settings

Acute Toxicity Studies

• Purpose is to evaluate the immediate toxic effects of a single, high dose of a drug
• Involves a single or multiple doses within 24 hours
• Typically uses two species, in which one is a rodent and one is a non-rodent.
• Duration is 14 days or longer, depending on the observed effects
• Determines the LD50 (Lethal Dose 50%), the dose that kills 50% of the test animals
• Identifies immediate side effects such as nausea, seizures, or organ failure

Subacute (Repeated Dose) Toxicity Studies

• Observes toxic effects from repeated exposure over a short period, usually 14-28 days
• Involves daily or multiple doses at different levels
• At least two species (e.g., rats and dogs) are used
• Helps determine the No Observed Adverse Effect Level (NOAEL), the highest dose with no toxic effect
• Assists in identifying target organs affected by repeated dosing

Chronic Toxicity Studies

• Assesses long-term toxicity caused by repeated drug exposure, often lasting for 3 to 12 months
• Commonly uses rats and dogs
• Monitoring includes blood work, organ function tests, body weight, and behavioral changes over time
• Identifies chronic toxic effects on specific organs or systems (e.g., heart, liver, kidneys)
• Helps predict cumulative toxicity or delayed onset side effects

Carcinogenicity Studies

• Determines if the drug has the potential to cause cancer after long-term exposure
• Usually conducted over 2 years in rodents
• Detects the formation of tumors in specific tissues
• Essential for chronic medications or those used for non-life-threatening conditions

Genotoxicity Studies

• Evaluates whether the drug can cause genetic mutations or damage DNA, which could lead to cancer or hereditary disorders

Reproductive and Developmental Toxicity Studies

• Assesses the drug's effects on fertility, pregnancy outcomes, and fetal development
• Detects risks such as reduced fertility, miscarriage, or birth defects.
• Includes the study of teratogenic effects, abnormalities in fetal development
• Essential for drugs intended for women of childbearing age or pregnant women

Immunotoxicity Studies

• Assesses if the drug adversely affects the immune system
• Identifies risks of immunosuppression (making the body vulnerable to infections)
• Detects potential for autoimmune responses (the immune system attacking healthy tissues)

Local Toxicity Studies

• Evaluates the local effects of the drug when applied to a specific site (e.g., skin, eyes, or injection site)
• Detects irritation, redness, or swelling at the site of administration
• Commonly used for topical creams, ophthalmic drugs, or injectable solutions

Repeated Dose Toxicity with Recovery Period Studies

• Determines if toxic effects observed during the dosing period reverse or persist after the drug is stopped
• Involves dividing animals into two groups, where one receives the drug continuously, while the other group stops dosing after a specific period to observe recovery
• Helps assess the reversibility of adverse effects
• Determines if the drug leaves permanent damage to organs or systems

Pharmacokinetics (PK) Studies

• Explores how the drug behaves inside the body by examining ADME (Absorption, Distribution, Metabolism, and Excretion)

Key Parameters of PK Studies

• Absorption: How quickly and how much of the drug enters the bloodstream
• Distribution: How the drug spreads throughout the body and whether it reaches the target tissues
• Metabolism: How the liver or other organs break down the drug
• Excretion: How the drug is eliminated from the body (e.g., through urine or feces)

Pharmacodynamics (PD) Studies

• Determines how the drug affects the body and confirm its mechanism of action

Key Aspects of PD Studies

• Mechanism of Action (MOA): Describes how the drug interacts with a target, such as a receptor or enzyme
• Dose-Response Relationship: Tests different doses to determine how much drug is needed to achieve the desired effect
• Therapeutic Index (TI): Ratio of toxic dose to therapeutic dose (A higher TI indicates a safer drug.)

In Vivo Animal Models

• Used to predict the drug's behavior and effects in humans

Types of Animal Models and Their Uses

• Rodents (Mice, Rats): Commonly used for toxicity and efficacy studies
• Rabbits