Pharmacokinetics: Designing and Optimizing Dosage Regimens

Key Components of Dosage Regimen

• Dose of the Drug: Amount to be administered.
• Dosing Interval: How often the drug is given (e.g., once daily, twice daily).
• Route of Administration: For example, oral (PO) or intravenous (IV).

Continuous Infusion

• Advantages: Simple to maintain therapeutic concentrations.
• Route: Typically IV.
• Graph Analysis:
  • Infusion increases drug concentration.
  • Eventually reaches a peak (steady state).
  • Steady State Concentration:
    • Dosing rate equals elimination rate (equilibrium).
    • Reached at a point where the concentration plateaus.
    • Achieved after 4-5 half-lives.

Half-Life

• Time required to reach steady state concentration is 4-5 half-lives.
• Time to eliminate 95% of the drug also takes 4-5 half-lives.

Maintenance and Loading Doses

Maintenance Dose

• Purpose: Maintain steady state concentration of the drug.
• Calculation:
  • Target plasma concentration x Clearance x Dosing interval / Bioavailability.
• Influences:
  • Clearance:
    • Affected by renal and hepatic function.
    • Reduced clearance requires modifying the maintenance dose.
  • Dosing Interval:
    • Changes in interval affect drug concentration; more frequent intervals maintain higher concentrations.

Loading Dose

• Purpose: Rapidly achieve peak serum concentrations, especially in critically ill patients.
• Calculation:
  • Target plasma concentration x Volume of distribution / Bioavailability.
• Influence of Volume of Distribution:
  • High volume requires higher loading doses.
  • Low volume requires lower loading doses.

Example Calculation

• Given a patient with specific body weight and desired plasma concentration.
• Use formulas to calculate the appropriate loading dose.
• Importance of understanding the relation between loading dose and volume of distribution.

Practical Considerations

• Adjust dosage regimens based on patient’s renal and hepatic function.
• Maintain awareness of the relationship between clearance and maintenance doses, and volume of distribution in loading doses.
• Importance of memorizing dosage formulas for calculations.