The volume of distribution is the apparent volume in which the drug can distributed in. It is the parameter that relates the amount of drug in the body to the concentration of the drug in the sampling site. It is not an actual volume, however it is a hypothetical volume determined by the drug distribution behavior.

The volume of distribution ranges from 3-5 liters to more than 25 L/kg. Drugs with higher affinity for tissues, have higher volume of distribution.

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.

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 CL_T(m) for the metabolite is constant within a patient (dose and concentration independent) when its elimination processes follow first-order kinetics.

The CL_T(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).

The amount of the metabolite formed after drug administration depends on the dose of the drug and f_m. If f_m 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 f_m values for each metabolite. The sum of these f_m values should not m m 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.