Pharmacokinetics Study Notes

Study Notes

dmpk Study Notes

Pharmacokinetics

Definition: The study of how drugs move through the body over time.
Key Phases:
1. Absorption: How a drug enters the bloodstream.
2. Distribution: How the drug spreads throughout the body’s tissues.
3. Metabolism: The body's chemical alteration of the drug.
4. Excretion: How the drug is eliminated from the body.

Drug Absorption

Influencing Factors:
- Formulation: Solid vs. liquid forms; pH levels.
- Route of Administration: Oral, intravenous, intramuscular, etc.
- Physiological Factors: Blood flow, surface area of absorption, gastric emptying time.
Mechanisms:
- Passive diffusion, facilitated diffusion, active transport, and endocytosis.

Metabolic Pathways

Phase I Reactions:
- Oxidation, reduction, hydrolysis.
- Enzymes involved: Cytochrome P450 family.
Phase II Reactions:
- Conjugation reactions (e.g., glucuronidation, sulfation).
- Involves transferases.
Importance: Determines the drug's efficacy and toxicity.

Bioavailability Studies

Definition: Measurement of the extent and rate at which the active ingredient or active moiety is absorbed and becomes available at the site of action.
Methods:
- Absolute Bioavailability: Comparison with an intravenous dose.
- Relative Bioavailability: Comparison with another formulation.
Key Parameters:
- Area under the curve (AUC), peak concentration (Cmax), time to peak concentration (Tmax).

Toxicity Evaluation

Purpose: To assess the adverse effects of drugs on biological systems.
Approaches:
- In vitro Studies: Cell line assays, enzyme inhibition studies.
- In vivo Studies: Animal models to evaluate systemic toxicity, organ-specific effects.
Assessments:
- Acute toxicity, chronic toxicity, reproductive toxicity, carcinogenicity.
Regulatory Considerations: Compliance with guidelines for preclinical and clinical testing.

Pharmacokinetics

Studies drug movement in the body over time, crucial for understanding drug action and safety.
Key phases include:
- Absorption: Entry of the drug into the bloodstream.
- Distribution: Dispersion of the drug across body tissues.
- Metabolism: Chemical transformation of the drug by the body.
- Excretion: Removal of the drug from the body.

Drug Absorption

Influenced by various factors:
- Formulation: Different drug forms (solid vs. liquid) affect absorption; pH levels can enhance or hinder effectiveness.
- Route of Administration: Options include oral, intravenous (IV), and intramuscular (IM), affecting bioavailability.
- Physiological Factors: Blood flow, absorption surface area, and gastric emptying rates significantly influence absorption.
Mechanisms of absorption:
- Includes passive diffusion, facilitated diffusion, active transport, and endocytosis, which determine how drugs cross membranes.

Metabolic Pathways

Divided into two phases:
- Phase I Reactions: Involve chemical changes such as oxidation, reduction, and hydrolysis, primarily mediated by Cytochrome P450 enzymes.
- Phase II Reactions: Involve conjugation processes (e.g., glucuronidation, sulfation), primarily performed by transferase enzymes.
Understanding metabolism is key to assessing a drug’s efficacy, safety, and potential toxicity.

Bioavailability Studies

Measures how much and how quickly active drug ingredients reach the site of action.
Types of bioavailability:
- Absolute Bioavailability: Evaluates drug absorption by comparing with an intravenous reference.
- Relative Bioavailability: Compares absorption of different formulations.
Key parameters assessed:
- Area Under the Curve (AUC): Reflects total drug exposure over time.
- Cmax: Maximum concentration of the drug in the bloodstream.
- Tmax: Time taken to reach Cmax, providing insights into absorption speed.

Toxicity Evaluation

Aims to determine the potential adverse effects of drugs on living organisms.
Approaches include:
- In vitro Studies: Use of cell lines and enzyme assays to examine drug effects on biological functions.
- In vivo Studies: Utilize animal models to evaluate overall toxicity, specific organ effects, and general safety.
Assessments cover different toxicity types:
- Acute toxicity, chronic toxicity, reproductive toxicity, and carcinogenicity.
Regulatory considerations ensure compliance with preclinical and clinical testing guidelines to promote safe drug development.

Description

Dive into the essential concepts of pharmacokinetics with these study notes. Learn about the key phases of drug movement in the body, including absorption, distribution, metabolism, and excretion. Explore the influencing factors and metabolic pathways that affect drug action.