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 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
- It follows that organ clearance as defined by flow and concentration
- 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
- 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.