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 metabolite total body clearance is the volume of the plasma or blood which is completely cleared from the metabolite per unit time. It has units of vloume/time.
The CLT(m) for the metabolite is constant within a patient (dose and concentration independent) when its elimination processes follow first-order kinetics.
The CLT(m) is a measure of the efficiency of all eliminating organs in eliminating the metabolite.
The metabolite elimination rate constant and the metabolite half life (the dependent pharmacokinetic parameters) are dependent on (is determined from) the metabolite total body clearance and the metabolite volume of distribution (the independent pharmacokinetic parameters).
CLT(m)
Vd(m) = k(m) andCLT(m)
Vd(m) =0.693
t 1/2(m)It is the integral of the plasma concentration-time profile from time zero to time infinity.
It has units of mass-time/volume.
The area under the curve after an iv administration is dependent on the administered dose and the total body clearance.
The amount of the metabolite formed after drug administration depends on the dose of the drug and fm. If fm is equal to unity (1) for a particular metabolite, this means that the entire dose of the parent drug is converted to that metabolite.
Drugs that undergo parallel metabolism to more than one metabolite have different fm values for each metabolite. The sum of these fm values should not be more than one, but it does not have to be equal to one (when the drug elimination involves a pathway other than metabolism).
This fraction should be dose independent when drug elimination follows first-order kinetics. Also, this fraction should not be different for a particular drug in a particular patient after different routes of administrations, if the metabolite is not formed during drug absorption after extravascular administration.
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.