PHA 5127

Basic Principles of Dose Optimization

INTRODUCTION

• DEFINITIONS:

• BIOPHARMACEUTICS deals with the influence of the dosage form of a drug on its pharmacological effectiveness.
  
• PHARMACOKINETICS deals with the time course of the drug and metabolite concentration in the body.
  

SIGNIFICANCE:

Which is the optimum way to treat a certain patient with a certain drug?

1. Which dose should be used?
2. Which dosage regimen should be used?
3. Which dosage form should be used?

OBJECTIVE:

What happens to a drug after its administration?

Fate of drug:

• Liberation
• Absorption
• Distribution "LADME"
• Metabolism
• Excretion
  

What does the drug do to the body

METHODS:

1. Measure drug and metabolite concentration in blood, urine and other body fluids as a function of time
2. Set up models to describe the time and to predict the drug levels at times not studied.
3. Determine parameters from model (half-life, clearance, volume of distribution etc.) which can be related to the physiological, clinical, physical or chemical properties of the drug.
4. Measure effect.

GOAL:

To produce a desired drug concentration in the body by choosing the optimum dosage regimen and dosage form.

PROBLEM:

• Correlation between pharmacokinetics and pharmacodynamics.
• Which drug level is desired?
• Patient variability
  

GENERAL PRINCIPLES

(Read also Martin, Physical Pharmacy, Chapter 1)

PHARMACEUTICAL SCIENCES