IC8

• Routes of drug administration


  • Oral
  • IV
  • Intramuscular
  • Subcutaneous
  • Topical
  • Nasal inhalation
  • Gargles
  • Buccal
  • Rectal
  • Sublingual
  • transdermal
• Cb


  Concentration in Blood
• C


  Plasma concentration
• Cu


  Concentration of unbound drug in the plasma
• Fu


  Fraction unbound (Cu/C)
• Blood consisting of RBCs, plasma and buffy layer
• Concentration of unbound drug in the plasma is laborious to get results
• Fraction unbound usually stays constant unless external factors affecting protein binding occurs
• Severe burns causing interstitial fluid leakage can affect protein binding
• Compartmental models


  • Representing a tissue or group of tissues with similar blood flow and drug affinity
• PK after IV bolus administration and linear kinetics


  1. First order kinetics

  2. Drug left in body as metabolism of drugs occurs and metabolism rate both decreases

  3. Vice versa
• Elimination rate constant


  Constant of proportionality involved in the proportional relationship between the rate of elimination changing as amount of drug preset in the body changes
• Elimination half-life


  Time taken for plasma drug concentration to decrease by half
• Assumptions for 1 compartment model: Drug distributes instantaneously and followed by rapid equilibrium
• Linear kinetics


  Dose proportionality in concentration and AUC (area under the curve)
• Clinical implications of linear kinetics: drugs following first-order kinetics means proportional changes with dosage and drug concentration and exposure in the body
• Graded dose-response curve


  • Indicates maximal efficacy of a drug
  • Linear scale
  • Semi-log scale
  • Saturable range: Small/no change in response
  • Log-linear range: Large change in response
• Quantal dose-response curve


  • All or none response, indicating potential variability of responsiveness among individuals
  • Relates the dose of a drug to the frequency in which a response occurs within a population
  • Can compare potency between drugs
• Response


  Pharmacological or toxicological effect from the action of a drug in the body
• Potency


  Same extent of effect but dosage required to bring about said extent of effect is different
• Efficacy


  Magnitude of maximum effect of same doses of drugs
• Therapeutic index


  • Reflects how selective the drug is in producing its desired effects versus its adverse effects
  • Used to estimate drug safety in humans
• Therapeutic window/therapeutic concentration range


  Limits of plasma drug concentrations expected to produce desired therapeutic effect with minimal adverse effects