Pharmacokinetics: Dosage Regimens

Key Concepts

• Designing & Optimizing Dosage Regimen: Crucial for determining:
  • Dose: Amount of drug to administer.
  • Dosing Interval: Frequency of administration (once, twice, or thrice daily).
  • Route of Administration: Oral (PO) vs. Intravenous (IV).

Continuous Infusion

• Easy to achieve therapeutic concentrations without complex calculations.
• Graph Representation:
  • Increasing drug concentration leads to a reach of peak plasma concentration.
  • Once the infusion stops, concentration decreases due to elimination.
  • Equilibrium: Achieved when dosing rate = elimination rate, resulting in a plateau known as steady-state concentration.
• Time to Steady State: Takes 4-5 half-lives to reach.

Steady State Concentration

• Occurs when dosing rate equals elimination rate.
• Concentration at steady state not dependent on half-life but on infusion rate.
  • Increase in infusion rate increases steady-state concentration.
  • Time to reach steady state remains 4-5 half-lives.

Maintenance Doses & Loading Doses

• Maintenance Dose: Required to maintain steady-state concentration.
  • Formula: Target plasma concentration x Clearance x Dosing Interval / Bioavailability.
  • Influences:
    • Dosing Interval: Proportional to drug concentration.
    • Clearance: If reduced (renal/hepatic dysfunction), decrease maintenance dose or alter dosing interval.
• Loading Dose: Used to achieve rapid therapeutic concentrations.
  • Formula: Target plasma concentration x Volume of Distribution / Bioavailability.
  • Volume of Distribution:
    • High volume requires higher loading dose for adequate plasma concentration.
    • Low volume requires lower loading dose.

Clinical Application

• Question Example: Calculation of an oral loading dose based on bioavailability, volume of distribution, and desired steady state concentration.
• Formulas: Vital for solving pharmacokinetic problems (plug and chug method).
• Understand relationships:
  • Loading dose ↔ Volume of Distribution
  • Maintenance dose ↔ Clearance

Summary

• Understanding dosages requires knowledge of pharmacokinetic principles and formulas.
• Steady state, maintenance doses, and loading doses all play specific roles in therapeutic drug management.
  • Steady State: Achieved when administration equals elimination after 4-5 half-lives.
  • Loading Dose: Quickly achieves desired concentration in critically ill patients.
  • Maintenance Dose: Maintains this concentration and is influenced by clearance and dosing intervals.

Important Relationships

• Loading Dose & Volume of Distribution: High distribution requires higher doses.
• Maintenance Dose & Clearance: Decreased clearance necessitates dose adjustment.

These concepts are crucial for exams and practical application in clinical settings.