Pharmacokinetics Overview

Pharmacokinetics

• Pharmacokinetics is the study of "what the body does to a drug"
• It differs from pharmacodynamics, which is the study of "what a drug does to the body"
• Pharmacokinetics involves the rate and extent of drug absorption, distribution, metabolism, and excretion
• It explains drug concentration fluctuations over time after administration
• It's critical for determining appropriate dosage regimens and predicting drug responses

Learning Outcomes

• Students should be able to explain
  • What pharmacokinetics is
  • How drugs are absorbed into the body
  • Drug distribution in the body
  • Drug metabolism in the body
  • Drug excretion from the body
  • Relationship between drug concentration and time (single dose)
  • Relationship between drug concentration and time (repeated doses)

Drug Absorption

• Drugs can be absorbed orally, buccally, sublingually, rectally, intravenously, intramuscularly, subcutaneously, or by inhalation
• Oral (PO) administration involves drug absorption across the small intestine's mucosa, then the portal circulation, and eventually systemic circulation
• Buccal or sublingual administration avoids portal circulation, with direct absorption into systemic circulation
• Intravenous (IV) injection delivers the drug directly into the bloodstream, bypassing absorption processes.
• Factors affecting absorption include route, drug properties (e.g., lipid solubility), and physiological conditions.

Drug Distribution

• For a drug to have its desired pharmacodynamic effects, it must reach its target site at an adequate concentration
• Distribution depends on factors like blood flow, drug properties, and special barriers (e.g., blood-brain barrier).
• Drug molecules move across cell membranes through processes like passive diffusion, facilitated diffusion, or active transport.
• Distribution influences drug action by affecting the concentration at the target site.

Drug Metabolism

• Metabolism, often in the liver, transforms drugs into metabolites
• It helps inactivating drugs and making them more water-soluble for excretion
• Metabolism can be categorized into Phase I (e.g., oxidation, reduction, hydrolysis) and Phase II (e.g., glucuronidation, sulfation, or acetylation) reactions
• Liver is the primary organ of drug metabolism due to high blood flow and presence of enzymes like Cytochrome P450 (CYP) system
• Interactions with other drugs or substances can influence metabolism.

Drug Excretion

• Kidneys are the major organ for excreting drug metabolites
• Drugs can be eliminated through glomerular filtration, tubular secretion, and tubular reabsorption
• Other routes include biliary excretion (into bile, then feces), respiration (for volatile drugs), sweat, and breast milk.
• Factors like urine pH and presence of other substances in the body may affect the rate of drug excretion
• enterohepatic circulation is also essential in eliminating drugs.

Concentration-Time Relationships (Single Dose)

• First-order kinetics: The rate of elimination is proportional to the drug concentration
• The rate of elimination is constant at a specific time interval (e.g. 50% decrease per hour)
• Describes the decrease in drug concentration over time
• Exponential decline in drug concentration in the plasma

Concentration-Time Relationships (Repeated Doses)

• Zero-order kinetics: A constant amount of drug is eliminated per unit of time
• The rate of elimination becomes saturated (e.g., enzyme systems are maxed, metabolite removal is limited by capacity)
• Elimination is not based on concentration and the accumulation of the drug may lead to undesirable concentrations and potential toxicity.