3.22:
Drug Elimination: The Concept of Clearance
Administered drugs circulate in the blood plasma until they are removed by the kidneys through urine or by the liver via bile. Drug clearance is a pharmacokinetic parameter that measures how efficiently the body removes the drug from systemic circulation within a specified time.
Drug clearance is measured as the rate at which a drug is eliminated from plasma divided by the plasma concentration of the drug. It is the most crucial parameter for designing a rational dosage regimen.
If the bioavailability of a drug is assumed to be 100%, clearance helps determine the dosing rate needed to achieve a steady-state concentration of the drug in plasma.
As long as the correct dosing rate is maintained, the body clears a constant fraction of the drug per unit of time. Increasing the drug concentration beyond the prescribed dosing rate overburdens elimination pathways and decreases drug clearance.
This raises plasma drug concentrations to toxic levels, leading to one or more adverse effects.
3.22:
Drug Elimination: The Concept of Clearance
Drug elimination refers to removing drugs from the body, either through urine by the kidneys or through bile by the liver. Drug clearance is a pharmacokinetic parameter that measures the efficiency of drug removal from the bloodstream within a specific time frame. It is calculated as the rate at which a drug is eliminated from plasma divided by the plasma concentration of the drug.
Drug clearance is not limited to renal excretion but encompasses all organs involved in drug elimination, including the liver, lungs, and biliary system. The sum of clearances by all eliminating organs is known as the total body or systemic clearance. It can be expressed as a combination of renal clearance and nonrenal clearance.
Understanding drug elimination kinetics and the concept of drug clearance is essential for designing effective dosage regimens and ensuring safe and optimal drug therapy. It allows for individualized adjustments based on a person's specific needs.
Exceeding the prescribed dosing rate can overload elimination pathways and decrease drug clearance. This leads to elevated plasma drug concentrations, which can result in toxic levels and cause adverse effects.