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.
When drug administration involves repeated doses, the drug concentration-time profile during each of the dosing intervals ( τ ) will be identical at steady state. This means that the maximum, the minimum, and the average concentrations during each dosing interval will be similar at steady state.
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 1/2The 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 1/2The 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.