Pharmacokinetics (PK)

• PK


  What the body does to the drug
• PK


  1. Involves stage of drug dose administration into the concentration in the blood

  2. Helps decide form and decision

  3. Helps to predict drug interaction potential

  4. The relationship between drug dose, concentration and time

  5. Dose and concentration in the blood
• Aspects of absorption, distribution, metabolism and excretion of a drug

  • Absorption
  • Distribution
  • Metabolism
  • Excretion
• Absorption


  1. Passage of drug from administration site into the plasma

  2. Drug must enter plasma before reaching the site of action

  3. Oral - absorption through the GI tract
• Factors affecting oral administration

  • GI motility (increase motility, and gastric stasis)
  • Gastric emptying (rapid emptying and slow emptying)
  • Splanchnic blood flow (blood flow to the stomach, spleen, pancreas, large intestine, small intestine and liver)
  • Particle size (large particle size means decreased absorption)
  • Formulation (capsules, liquids, sustained release delay absorption, enteric coating)
• Barriers to systemic absorption

  • Degraded in the lumen
  • Metabolised by CYP3A4
  • Metabolised in portal blood
  • Metabolised or excreted in the liver
• Distribution


  How a drug moves around the body to reach its target after it is in the systemic system, occurs after the drug reaches the circulation through body fluids and fats
• Aspects of distribution


  • Plasma protein binding - unbound drug binds to proteins to form drug protein complex (unbound is eliminated)
  • Tissue accumulation (drugs have high affinity for tissues and can accumulate)
  • Volume distribution - the volume of fluid required to contain the total amount of drug in the body at the same time concentration as the present in the plasma
• Drugs with small VD

  Shorter half-lives, accumulate less in the body, require loading dose
• Drugs with higher VD


  Longer half lives, accumulate more in the body
• Metabolism


  1. Elimination (metabolism and excretion)

  2. The drug becomes more polar (hydrophilic) and hastens excretion by the kidneys

  3. Enzyme metabolism enhance CYPs and speed up metabolism, enzyme inhibitors reduce effects of CYPs and slow down metabolism
• Routes of elimination


  • Metabolism- metabolic transformation
  • Liver - main source of metabolism
  • Intestine, kidney, lung
  • Renal (urine) - Glomerular filtration, tubular reabsorption, tubular secretion
  • Biliary (faeces)
  • Exhalation
• Factors affecting absorption


  • Route of Administration
  • Physicochemical Properties of the Drug
  • Drug Formulation
  • Blood Flow to Absorption Site
  • Surface Area Available for Absorption
  • Gastrointestinal Tract Factors
  • Patient Factors
  • Interactions with Other Substances
  • First-Pass Metabolism
• Routes of administration


  • Oral
  • Intravenous (IV)
  • Intramuscular (IM)
  • Subcutaneous (SC)
  • Topical
  • Sublingual/Buccal
  • Inhalation
• Physicochemical Properties of the Drug

  Solubility, Ionization, Molecular Size
• Drug Formulation


  Solid vs. Liquid, Enteric Coating, Sustained-Release
• Blood Flow to Absorption Site

  Increased Blood Flow, Decreased Blood Flow
• Surface Area Available for Absorption

  Larger Surface Area, Smaller Surface Area
• Gastrointestinal Tract Factors


  • Gastric Emptying Time
  • Gastric pH
  • Presence of Food
• Patient Factors


  • Age
  • Health Status
  • Genetics
  • Hydration and Electrolyte Balance
• Interactions with Other Substances

  • Other Medications
  • Food
  • Herbal Supplements
• First-Pass Metabolism


  Liver Metabolism - Drugs absorbed from the gastrointestinal tract first pass through the liver where they can be metabolized, reducing the amount of active drug reaching systemic circulation
• Phases in hepatic metabolism

  • Phase I: Functionalization
  • Phase II: Conjugation
  • Phase III: Transport/Elimination
• Half-life of a medicine

  The time taken for plasma concentration or amount of drug in body to decrease to 50%
• Importance of half-life


  • Dosing Schedule
  • Steady-State Concentration
  • Duration of Action
  • Drug Clearance
  • Adjusting Dosages
  • Managing Side Effects
  • Drug Interactions
  • Patient Compliance
• CYP450 metabolic pathway


  • Enzyme Activation - The CYP450 enzymes are activated when a drug enters the liver through the bloodstream
  • Metabolism - The activated enzymes chemically modify the drug, often making it more water-soluble so that it can be excreted from the body through urine or bile
  • Drug Interactions - Some drugs can inhibit or induce CYP450 enzymes, affecting the metabolism of other drugs
• Pharmacokinetic Interactions


  • Absorption
  • Distribution
  • Metabolism
  • Excretion
• Pharmacodynamic Interactions


  • Additive Effects
  • Synergistic Effects
  • Antagonistic Effects
• Volume of distribution (Vd)

  0% accumulates less in the body, has shorter half-life, may require loading dose, requires more frequent dosing, essential for monitoring drug levels in the bloodstream
• Bioavailability


  Refers to the fraction of the administered dose of a drug that reaches the bloodstream in its active form
• Bioequivalence


  Refers to the similarity in the rate and extent of drug absorption between two formulations of the same drug
• First-pass metabolism


  Metabolism of a drug that occurs before it reaches systemic circulation, usually in the liver
• Factors affecting distribution


  • Characteristics of the drug (permeability, binding within compartments, physical properties of drug – molecular weight, lipophilicity, polarity)
  • Physical factors (regional blood flow, cardiac output, capillary permeability, tissue volume)
• Elimination process via the kidney


  1. Filtration

  2. Reabsorption

  3. Secretion

  4. Excretion
• CYP substrate


  A drug that is metabolized by a specific CYP enzyme
• CYP inducer


  A substance that increases the activity of a specific CYP enzyme, leading to faster metabolism of drugs that are substrates for that enzyme
• CYP inhibitor


  A substance that decreases the activity of a specific CYP enzyme, leading to slower metabolism of drugs that are substrates for that enzyme
• Identifying potential pharmacokinetic (PK) interactions involving CYP enzymes involves understanding which drugs are substrates, inducers, or inhibitors of specific CYP enzymes