A first-order process is a process that has a rate proportional to the amount of the reactant involved in this process.
For example, if the drug elimination rate is proportional to the amount of the drug in the body, this means that this drug is eliminated by a first-order process. The proportionality constant is the first-order elimination rate constant. i.e.
Elimination rate = elimination rate constant x drug amount
The rate of drug elimination decreases with time because the amount of the drug remaining decreases with time.
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 1/2When the plasma concentration-time profiles after administration of different doses are plotted on a semilog scale, the graph may not clearly illustrate the proportionality between the dose and the resulting AUC due to the nonlinear nature of the semilog scale. The proportionality between the dose and the AUC will be very clear on a linear scale.