The first-order elimination rate constant of the metabolite is the rate constant responsible for the elimination of the metabolite from the body. This rate constant is dependent on the clearance and the volume of distribution of the metabolite. (CL_T(m)) / Vd_(m) = k_(m))

The elimination rate constant of the metabolite is the same when the metabolite is formed in vivo after the parent drug administration and after administration of the preformed metabolite.

This constant represents the metabolite elimination through all routes of metabolite elimination including secondary metabolism and renal excretion.

The first-order elimination rate constant of the metabolite has units of time ^-1.

The metabolite elimination rate constant for formation rate limited metabolites can be determined if enough samples are available during the formation of the metabolite.

a- Back extrapolate the metabolite terminal phase until it intersect with the y-axis.

b- Calculate the residuals value during the metabolite formation phase. (the residuals are the difference between the value of the metabolite conc and the corresponding values at the same time on the extrapolated line)

c- Plot the residuals versus time. The slope of the line will be equal to (-k_(m)/2.303)

d- The half life of the metabolite can be determined from the residuals versus time plot.

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.