Higher doses result in higher amounts excreted in urine. However the rate of decline of the renal excretion rate does not change because it depends on k (k =CLT/Vd)
Larger amount of the drug is recovered in urine after administration of larger doses. However, the fraction of the dose excreted in urine is constant because the ratio of CLR/CLT is constant
Doseis the administered dose of the drug (amount).
CLTis the total body clearance (volume/time).
CLRis the renal clearance (volume/time).
Renal Clearance
It is the volume of the plasma or the blood that is completely cleared from the drug per unit time by the kidney. It has units of volume/time.
The renal clearance cannot exceed the CLT. However it can be equal to the CLT when the drug is excreted completely unchanged by the kidney.
The renal clearance can be determined from the renal excretion rate over a short interval and the average plasma concentration during this interval.
Renal clearance =
Renal excretion rate
Cp average
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).
