Pharmacokinetics: the mathematical analysis of all drug disposition factors (absorption, distribution, metabolism, and excretion)

Basic concepts

• A simple starting point is to consider the human body as a single, well stirred, compartment of volume Vd
• Drug is added to the compartment by absorption at rate ka and removed by elimination at rate ke
• If drug at dose D is added rapidly by IV absorption is by-passed
• The initial concentration (C0) = D/Vd (concentration = mass/volume)
• The concentration at a later time t (Ct) will depend on ke
  • ke (the elimination rate constant) is the fraction of the amount of drug in the body (A) that is eliminated per unit time
  • In general rate of elimination = ke x A

First order kinetics

• Most drugs exhibit first-order kinetics where the rate of elimination is directly proportional to drug concentration

• For drugs that exhibit first order kinetics, the dose administered changes Cp in direct proportion, but does not affect ke or t1/2

Clearance

• Clearance: the volume of plasma cleared of a drug in unit time
• Determines the maintenance dose rate (dose per unit time required to maintain a given plasma concentration)
• It is the sum of all clearance processes (renal + hepatic + other)

Factors influencing drug elimination

• Kidneys are the principle organ - renal filtration
  • Drug metabolites rendered polar by phase II metabolism - can’t be reabsorbed by the renal tubules and so are excreted in urine
• Drug concentration changes over time in the body - absorption and elimination occur simultaneously