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 CL_T 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. CL_T 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 and

CLT

Vd =

0.693

t 1/2

The volume of distribution is the apparent volume in which the drug can distribute in. It is the factor 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.

The first-order elimination rate constant is the rate constant for the elimination of the drug from the body. The elimination rate constant and the half life are dependent on the total body clearance and the volume of distribution of the drug.

CLT

Vd = k =

0.693

t 1/2

This rate constant represents drug elimination through all routes of drug elimination such as metabolism, renal excretion, and other routes.

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

The half life is the time required for the amount of the drug or the plasma concentration of the drug to decrease by 50%. The half life has units of time.

The half life and the first order elimination rate constant are dependent on the total body clearance and the volume of distribution.

CLT

Vd = k =

0.693

t 1/2

The half life of a drug is constant within a patient (dose and concentration independent) when the drug elimination process follows first-order kinetics. However different patients may have different half lives for the same drug.

The half life is a very important parameter, because it indicates how fast the drug is eliminated from the body. Drugs with shorter half lives are eliminated faster than those with longer half lives.