Pharmacokinetics Overview

Pharmacokinetics

• Pharmacokinetics (PK) is the study of how a drug moves through the body
• Four main processes:
  • Absorption: Drug enters the bloodstream
  • Distribution: Drug travels through the bloodstream to its target
  • Metabolism: Drug is chemically modified usually to render it inactive
  • Excretion: Drug and its metabolites are removed from the body
• Variability exists between patients due to genetics, disease, and age
• ADME is a mnemonic to remember the four processes (Absorption, Distribution, Metabolism, Excretion)

The ADME Process

• Administration: Site of drug administration, common route is oral (GI tract)
• Absorption: Drug release and dissolution in GI fluid, permeation into the bloodstream
• Distribution: Movement of drug through bloodstream to target cells or tissues
• Metabolism: Chemical modification of drugs in the body (often in the liver) to make them easier to excrete
• Excretion: Removal of drug and metabolites from the body (usually kidneys/liver)

Absorption

• Definition: Movement of a drug from its administration site into the bloodstream
• Topical: Through skin or mucous membranes
• Oral: Through stomach or intestines (influenced by food)
• Mechanisms:
  • Passive Transport: Diffusion through cell membranes
  • Active Transport: Requires energy to move drugs through membranes
• Bioavailability: The proportion of a drug that successfully enters systemic circulation.

Distribution

• Definition: Movement of drugs through the bloodstream to their target cells or molecules.

• Factors:

  • Plasma Proteins: Drugs can bind to proteins in the blood, limiting their availability to target cells. . Blood-Brain Barrier: Blocks certain substances from entering brain tissue. . Blood-Placental Barrier: Regulates passage of substances from a pregnant woman's bloodstream to the fetus. . Blood-Testicular Barrier: Limits drug access to the testes.

Metabolism

• Definition: Chemical modification of drugs by enzymes, typically to inactivate them for excretion.
• Key processes:
  • Occurs in the liver (especially for oral administration)
  • First-pass effect: Oral drugs are extensively metabolized during their first pass through the liver, reducing their bioavailability.

Excretion

• Definition: Removal of drugs and their metabolites from the body
• Pathways:
  • Urination (primary pathway via kidneys)
  • Defecation
  • Exhalation (for gaseous forms)
  • Sweating and saliva (minor pathways)
• Kidneys: Important for filtering harmful substances and waste products.

Other Important Concepts

• Bioavailability: Fraction of administered drug reaching systemic circulation.
• First-pass effect: Reduction in bioavailability due to metabolism in the liver.
• Enterohepatic recirculation: Circulation of biliary acids back to the liver.
• P-glycoprotein: A transporter protein that pumps drugs out of cells, decreasing absorption.