elimination of a drug from a defined region of the body to the plasma concen-
tration of that drug. For example, the total clearance (ClT), that is, the volume
of blood in the whole body cleared of a drug in unit time, is related to the rate of
elimination by the equation:
rate of elimination of a drug from the whole body¼ClTCp (8:8)
The clearance of a drug from a specific region of the body is the sum of all
the clearances of all the contributing processes in that region. For example,
hepatic clearance (ClH) is the sum of the clearances due to metabolism (ClM) and
excretion (ClBile) in the liver, that is:
ClH¼ClMþClBile (8:9)
However, it is emphasized that clearance is an artificial concept as it is not
possible for a drug to be removed from only one part of the total volume of the
blood in the body or organ.
For elimination processes exhibitingfirst order kineticsit can be shown that
clearance is related toVd,kelandt1/2by the mathematical expressions:
ClT¼kelVd (8:10)
and
ClT¼Vd
0 : 693
t 1 = 2
(8:11)
Since botht1/2andkelare constant for elimination processesfollowing first
order kinetics, Cl will also be constant. However, should the order of the
elimination change due to a change in the biological situation, such as the
drug concentration increasing to the point where it saturates the metabolic
elimination pathways, then clearance may not be constant.
For an IV bolus, which places the drug directly in the circulatory system, total
clearance (ClT) of the drug from the body can also be determined from the plots
ofCpagainstt. The area under the curve (AUC) represents the total amount of
the drug that reaches the circulatory system in timet. It is related to the dose
administered by the relationship:
dose¼ClTAUC (8:12)
This relationship holds true regardless of the way in which a single dose of the
drug is administered. However, for enteral routes the dose is the amount
INTRAVASCULAR ADMINISTRATION 167