It is the integral of the plasma concentration-time profile from time zero to time infinity.
It has units of mass-time/volume.
The metabolite area under the curve after a single administration is dependent on the amount of the metabolite formed in vivo and the metabolite total body clearance.
The area of the trapezoid shown in the figure is equal to the area of a rectangle that have a similar width and a height of (a+b)/2
Area of the trapezoid = average height x width
a+b
2 ) .(W)The formation clearance of the metabolite is the fraction of the drug total clearance which is responsible for the formation of the metabolite. It is the product of the drug CLT and the fraction of the drug dose converted to the metabolite (fm).
When all the administered drug dose is metabolized to one metabolite, the formation clearance should be equal to the CLT of the drug (fm = 1).
When multiple metabolites are formed by parallel metabolism, each metabolite will have its own formation clearance. The sum of the formation clearances for all metabolites should not be more than the drug total clearance. However, the sum of the formation clearances of the metabolites will not be equal to the drug CLT if the drug elimination involves pathways other than drug metabolism.
The total body clearance is the volume of the plasma or blood which is completely cleared from the drug per unit time. It has units of volume/time.
The CLT for a drug is constant within a patient (dose and concentration independent) when the elimination processes follow first-order kinetics.
The total body clearance is a measure of the efficiency of all eliminating organs in eliminating the drug and it is the sum of all organ clearances (i.e. CLT is the sum of the renal clearance, hepatic clearance and all other organ clearances).
The elimination rate constant and the half life (the dependent pharmacokinetic parameters) are dependent on (is determined from) the total body clearance and the volume of distribution (the independent pharmacokinetic parameters).
CLT
Vd = k andCLT
Vd =0.693
t 1/2The first-order elimination rate constant is the rate constant for the elimination of the drug from the body. The elimination rate constant and the half life are dependent on the total body clearance and the volume of distribution of the drug.
CLT
Vd = k =0.693
t 1/2This rate constant represents drug elimination through all routes of drug elimination such as metabolism, renal excretion, and other routes.
The first-order elimination rate constant has units of time-1.