3.4. Pharmacokinetic Parameters

We will start this section with some more definitions.

Area under the Drug Concentration Curve or
If a plot of the plasma drug concentration versus time is made, then the area under this curve, or represents the total amount of drug absorbed. This parameter is very important in defining how well the drug is absorbed, and is required by the FDA in the drug approval process.
AUC of (Time x Plasma Drug Concentration) versus Time or
This is a related parameter to the one above, and represents the concentration of drug in the plasma or body.
 
Volume of Distribution,Vd
The volume of distribution is a purely kinetic parameter that is used to estimate the degree to which a drug permeates the different fluid compartments of the body. It is defined as the amount of drug in the body divided by the concentration of drug in the blood or plasma. The value can be derived graphically from plasma concentration versus time curves.

Clearance
Clearance of a drug from the body may be expressed as total body clearance or clearance form a specific organ such as the kidney or from the plasma. It is defined as the rate of elimination divided by the concentration:

 

Plasma Clearance
The volume of plasma cleared of drug per unit time as a result of all elimination pathways is known as the plasma clearance. If drug is eliminated by a first order rate constant kel, then:

 

Renal Clearance
The volume of plasma cleared of drug by the kidneys per unit time, is known as the renal clearance. It can be determined from measurements of the amount of drug voided in the urine and the plasma drug concentration.

 

Plasma Half Life
The biological or plasma half life of a drug is the time it takes for the plasma drug concentration to drop to one half. For the situation of equation (3.3) above, the half life can be shown to be related to the kel by:

It also follows that:

 

Single organ Elimination rate
Rate at which drug is cleared from an organ is known as the elimination rate.

It follows that organ clearance as defined by flow and concentration is:

 

Extraction Ratio
The difference between the inlet concentration and the outlet concentration, divided by the inlet concentration for an organ is known as the extraction ratio, and it defines the degree to which the drug is eliminated or degraded by that organ.

 

Oral Availability
The oral availability describes how much of a drug is available after having passed through the liver, and undergone the first pass effect, assuming 100% absorption.

The extraction ratio, and hence the oral availability of a drug can be calculated by measuring the AUC for the drug administered by IV injection, and knowing the blood flow rate through that organ. By comparing this value with that obtained for oral availability one can get and idea about the efficiency of the absorption process, or about the liver metabolism. An oral availability less than predicted suggests poor absorption, while one greater than predicted indicates that the liver metabolism may be via a mechanism that is saturable at high drug concentrations.