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.
It is the integral of the metabolite 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 drug 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)Administration of the preformed metabolite means obtaining the metabolite in large quantity (by chemical synthesis or by any other mean) that can allow administration of this metabolite to volunteers or to patients. Administration of the metabolite can be useful in assessing the pharmacological and toxicological effects of the metabolites and also in the determination of the metabolite pharmacokinetic parameters.
Before administration of the metabolite to patients or volunteers, it is important to make sure that the metabolite under investigation is safe. This is because some metabolites are known to be very toxic.