Unit volume of blood which is cleared off a drug per unit time is known as clearance.
Rate of elimination =Quantity or volume of urine measured (ml/min) X conc. substances in urine (mg/ml)
Rate of elimination = ml/min x mg/ml
Rate of elimination of a substance in urine is denoted by ROE. Clearance is the rate of elimination of substance in urine divided by the concentration in the plasma/blood.
Clearance = mg/min / mg/ml
Total clearance = CL kidney + CL liver + CL…..
Factors affecting Clearance:
- Inherent ability of the clearing organ to eliminate the drug. Any disease process might interfere.
- Blood flow to the organ- which sometimes is dependent on cardiac output. In severe cases functions of excretory organs might be affected.
Importance of Clearance
CL = ROE/Conc.
ROE = CL x Conc.
Organs when not diseased and drugs within therapeutic limits, the clearance remains constant. Thus, the rate of elimination is directly proportional to the concentration of the drug. This is in fact, first order kinetics which most of the drugs follow.
Once the plateau is reached, the zero order kinetics is followed, which may not be in the therapeutic range.
All drugs effect a person at certain concentrations. This concentration is known as target concentration. It is achieved only after four to four and a half, half lives. This is also known as the steady state. In order to achieve this, we determine the dosage rate.
Rate of administration = Rate of elimination
ROA = ROE
ROA = CL x C
Thus the dosage rate can be found. Most important parameter is the clearance. If clearance is affected, diseased state may lead to toxicity.
Four things determine the pharmacokinetic parameters for dosage rate:
- Clearance- most important parameter which needs to be adjusted in diseases of kidneys, liver to lower levels
- Volume of distribution
- Plasma half life
Two things can be said inexplicably
- Excretion is the excretory process
- Clearance is how efficient excretory processes are.