Pharmacokinetics 5 - Excretion

Excretion of Drugs in Pharmacokinetics

Overview of Drug Excretion

• This tutorial is the fifth in a pharmacokinetics series, focusing on drug excretion, defined as the irreversible removal of drugs from the body.

• Two primary excretion pathways are discussed: the hepatobiliary system (e.g., bile and feces) and renal excretion via kidneys, which will be the main focus.

Renal Excretion Process

• In renal excretion, drugs are filtered into the nephron of the kidney and eventually eliminated through urine.

• Key values include:

• CP: Concentration of drug in plasma.

• CUU: Concentration of drug in urine.

• VU: Rate at which urine is produced.

Understanding Clearance

• The formula for clearance is given by:

[

textClearance = CUU times VU/CP

]

• Conceptually, clearance indicates how much plasma contains a specific amount of drug being cleared over time.

Factors Affecting Drug Clearance

• Plasma concentration relates to drug dosage; higher doses lead to increased plasma concentrations.

• Urine production volume correlates with glomerular filtration rate (GFR); lower GFR due to kidney disease results in reduced clearance.

Drug Behavior in Nephron

• Drugs can either be reabsorbed or secreted within the nephron:

• Reabsorption decreases urinary concentration and clearance.

• Secretion increases both urinary concentration and clearance (e.g., penicillin).

Kinetics of Drug Excretion

First Order Kinetics

• Higher plasma concentrations result in faster excretion rates; this relationship creates a curve where elimination slows as plasma concentration drops.

Zero Order Kinetics

• When enzyme saturation occurs due to excessive drug levels, excretion becomes independent of plasma concentration, leading to linear kinetics instead of exponential decay.

• An example includes ethanol metabolism, where approximately 10g/hour is metabolized regardless of intake level.

Conclusion on Drug Elimination Patterns