WK 5 - 1 Lecture_Pharmacokinetics_Intro

Pharmacokinetics Overview

Presented by Robiul Islam, PhD, Pharmacy, College of Medicine and Dentistry.

Learning Objectives

• Core Principles of Pharmacokinetics:

  • Understanding absorption, distribution, metabolism, and elimination (ADME).

  • Clinical applications of pharmacokinetics in optimizing drug therapy.

  • Organs involved in ADME including the gastrointestinal tract (GIT), liver, skin, circulation system, and kidneys, and their respective roles in drug handling.

What is Pharmacokinetics?

Pharmacokinetics is the scientific study devoted to understanding the time course of a drug's movement through the body. Its primary focus is on how the body processes a drug, including its absorption, distribution, metabolism, and elimination, which are integral processes in determining the drug’s efficacy and safety. Additionally, Pharmacokinetics supports Therapeutic Drug Monitoring (TDM), which helps in individualizing drug therapy according to specific patient needs.

Key Concepts of Pharmacokinetics (PK)

ADME Process:

• Absorption: Refers to how drugs enter the bloodstream after administration; influenced by factors like formulation, route of administration, and the presence of food.

• Distribution: Describes the dispersion of drugs throughout body tissues, influenced by blood flow, tissue permeability, and binding to plasma proteins.

• Metabolism: Encompasses the biochemical modification of drugs primarily by enzymatic activity, mainly occurring in the liver. This process converts drugs into more water-soluble forms to facilitate excretion.

• Excretion: Involves the removal of drugs from the body, predominantly through the kidneys but also via bile, sweat, and respiratory pathways.

PK data provide essential insights that simplistically represent intricate physiological processes, making it a critical aspect of drug therapy.

Pharmacokinetics vs. Pharmacodynamics

• Pharmacokinetics (PK): Encompasses the processes of drug absorption, distribution, metabolism, and elimination and how these processes affect drug levels at the target sites over time.

• Pharmacodynamics (PD): Examines the physiological effects of drugs, including the mechanisms of action at receptor sites, which helps in understanding the drug’s therapeutic and toxic effects.

Routes of Drug Administration

Methods:

• Several methods of administration exist, including oral, intravenous (IV), intramuscular (IM), subcutaneous (SC), and inhalation. Each of these routes significantly influences the speed and efficiency of drug absorption and distribution within the body.

Administration Pathway Visualization:

• The administration pathway illustrates the journey of drugs from the site of administration to their systemic circulation and target sites, showcasing the factors affecting bioavailability.

Distribution of Drugs

General Concepts:

• Any organ or tissue can be involved in the distribution of drugs, considering blood acts as the primary transport medium. Factors such as tissue binding affinity and blood flow rates are critical in understanding how long a drug remains effective.

Models:

• Single-compartment Model: Assumes the body behaves as a single well-mixed reservoir.

• Two-compartment Model: Distinguishes between central and peripheral compartments to explain drugs that distribute more slowly or into specific sites. Understanding these models helps in accurate dosing and predicting drug behavior in different populations.

Drug Metabolism

Process:

• The metabolism process is vital for converting drugs into more hydrophilic forms to facilitate their excretion, primarily through renal pathways.

Phases of Metabolism:

• Phase I: Involves oxidation reactions, typically occurring through Cytochrome P450 enzymatic pathways, which modify drugs by introducing functional groups.

• Phase II: Comprised of conjugation reactions (like glucuronidation) that help in detoxifying and enhancing the excretion of drugs. Major sites for these metabolic processes predominantly include the liver, with extrahepatic metabolism observed in kidneys, lungs, and intestines.

Drug Elimination

Via Kidneys:

• Glomerular filtration requires drugs to be free of proteins and of a small molecular size. Understanding factors that influence glomerular filtration is critical in assessing drug elimination efficiency.

Methods of Elimination:

• Drugs are eliminated not just through urine but also through bile, expiration (as gases), and other routes like sweat or saliva, each contributing differently to the overall drug clearance profile.

Excretion Mechanisms

Three Processes:

• Glomerular Filtration: Filters unbound drug molecules from the plasma into urine formation.

• Tubular Secretion: Actively secretes unwanted drug molecules into the renal tubules, primarily in the proximal tubules.

• Tubular Reabsorption: Involves reabsorption of substances back into the bloodstream through passive or active mechanisms, critical for regulating drug levels during elimination.

• The renal excretion rate is explicitly determined by the interplay amongst these three processes, which are fundamental for understanding individual variability in drug clearance.

Skin as a Route for Drug Absorption

• Absorption through skin can occur via multiple pathways: transcellular, intercellular, and dermal layers. Small drug molecules also may undergo metabolic transformations and elimination processes through the skin, illustrating its role as a potential route for both absorption and excretion.

Clinical Applications of Pharmacokinetics

• Pharmacokinetics has significant applications in drug development and formulation evaluation, ensuring efficient and safe dosing regimens. It plays a pivotal role in therapeutic drug monitoring, helping healthcare providers adjust dosages and optimize patient outcomes based on individual body responses to medications.

References

• Hedaya MA (ed). Basic Pharmacokinetics (2nd edition