CritIC Pharmacokinetics Series: Clearance and Half-Life

Introduction

• Focus on clearance and half-life in drug pharmacokinetics.
• Drug elimination occurs through metabolism, excretion, or both.
• Detailed liver and kidney processes will be discussed in future videos.

Clearance

• Definition: Amount of plasma from which a substance is completely removed per unit time.
  • Unit: Volume per time, not concentration per time.
• First Order Kinetics: Clearance remains constant despite changes in drug concentration.
  • Example: A bucket of water with varying drug particles, clearance remains the same.
• Importance:
  • Helps calculate maintenance dose to maintain specific plasma levels.

Half-Life

• Definition: Time required for drug concentration in plasma to decrease by half.
• Steady State:
  • Discontinuation leads to reduced drug concentration over time.
  • After 5 half-lives, approximately 96.875% of the drug is cleared.
  • Reaching steady state also takes about 5 half-lives.
• Uses:
  • Calculating time to reach steady state.
  • Determining time to clear drug from the body.
  • Predicting changes in drug concentration when clearance or volume of distribution is affected (e.g., renal failure).

Impact of Renal Failure on Half-Life

• Renal Clearance: If renal function is impaired, half-life increases.
  • Example: A drug cleared 50% by liver and kidney each. Renal failure reduces renal function by half:
    • Liver clearance: 50% remains constant.
    • Renal clearance: Reduced to 25% (half of 50%).
    • Total clearance becomes 75%, increasing half-life by 33%.
• Dose Adjustment: May be required depending on the drug characteristics and patient condition.

Conclusion

• Upcoming videos will address metabolism and excretion details.
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