The same drug can have different CLT in different individuals due to differences in the function of the eliminating organ(s). Administration of the same infusion rate of the drug to patients with different CLT will produce higher steady state drug conc in patients with lower CLT.
Lower CLT results in higher steady state concentration when the infusion rate is kept constant.
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.
Steady state
The steady state is the condition when the rate of drug administration is equal to the rate of drug elimination.
When the drug is administered as a constant rate IV infusion, there will be one steady state concentration as long as the rate of administration and the rate of elimination do not change.
The time required to achieve steady state is dependent on the drug half life. It takes about 5-6 half lives to achieve steady state. The steady state concentration during constant rate iv infusion is directly proportional to the infusion rate and inversely proportional to the total body clearance of the drug.
Total body clearance (CLT)
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).
