Lecture Notes: Drug Clearance

Definition of Drug Clearance

• Clearance Definition: Rate of elimination of a drug divided by the plasma concentration of the drug.
• Formula: Volume of plasma cleared of the drug per unit time (volume/time).

Elimination vs. Excretion

• Elimination:
  • Combination of metabolism (primarily by the liver) and excretion (primarily by the kidneys).
• Excretion:
  • Removal of substances from the body, primarily through the urinary system.

Organs Involved in Clearance

• Primary Organs:
  • Kidneys
  • Liver
• Other Organs:
  • Lungs (e.g., anesthetics)
  • Gastrointestinal tract (GIT)
  • Excretion through breast milk, saliva, and lacrimal secretions.

Impact of Organ Dysfunction

• Renal Dysfunction:
  • Decreases clearance, leading to potential drug accumulation.
• Liver Dysfunction:
  • Also decreases clearance, affecting drug elimination.

Mathematical Equivalence in Clearance

• Clearance and Half-life:
  • Clearance is inversely proportional to the drug's half-life.
  • Equation: Clearance = (Volume of distribution * 0.7) / Half-life.*

Drug Half-life

• Definition: Time it takes for the drug concentration to reduce from 100% to 50%.
• Relationship with Clearance:
  • Longer half-life = lower clearance.
  • Shorter half-life = higher clearance.

Elimination Kinetics

• First-order Kinetics:
  • Most drugs follow this.
  • Characteristics:
    • Constant fraction of drug eliminated per unit time.
    • Exponential decline curve.
    • Rate of elimination is directly proportional to drug concentration.
• Zero-order Kinetics:
  • Few drugs follow this (PEA: Phenytoin, Ethanol, Aspirin).
  • Characteristics:
    • Constant amount of drug eliminated per unit time (linear decline).
    • Rate of elimination is independent of drug concentration.
    • Risk of toxicity due to saturation (Vmax).

Steady State and Half-life

• Steady State Concentration:
  • Achieved when the rate of drug administration equals the rate of elimination.
  • Takes approximately 4-5 half-lives to reach steady state.

Clinical Implications

• Dose Adjustments:
  • Renal or liver dysfunction requires dose adjustments to prevent drug accumulation.
  • In cases of increased half-life due to decreased clearance, dose should be reduced.

Practical Example

• Case 1: Renal disease affecting clearance, necessitating lower doses.
• Case 2: Calculation of time to reach steady state for a drug with a half-life of 12 hours (approximately 48 hours).

These notes summarize the key points from the lecture on drug clearance, providing a concise reference for understanding the main concepts and their clinical applications.