Chapter 6
Pharmacokinetics: Drug Excretion and Clearance
Drug Elimination: Overview
When drugs enter the body, they eventually undergo irreversible elimination. Drug elimination primarily involves excretion and metabolism or ...
Elimination Kinetics: First-Order and Zero-Order
A drug that enters the body is eliminated in due course, primarily via the kidneys.
Clearance is a pharmacokinetic parameter, relating a drug's ...
Renal Drug Excretion: Overview
The kidneys are primary excretory organs, filtering waste products from the bloodstream and excreting them into urine.
The kidneys efficiently eliminate ...
Renal Drug Excretion: Glomerular Filtration
In kidneys, drugs enter the renal artery, pass through the afferent arterioles, and drain into the glomerular capillaries surrounded by the Bowman's ...
Renal Drug Excretion: Tubular Reabsorption
After glomerular filtration, substances in the tubular lumen transport back into the bloodstream via tubular reabsorption.
Nutrients are actively ...
Renal Drug Excretion: Tubular Secretion
Blood exits glomeruli via efferent arterioles, reaching the capillary plexus surrounding the proximal tubule.
Here, unfiltered drugs are secreted into the ...
Renal Drug Excretion: Effect of Urine pH, Flow Rate, and Drug pKa
Urine pH and a drug's pKa determine its percentage ionization, which influences renal reabsorption and elimination.
Urine pH depends on diet, drug ...
Hepatic Drug Excretion: Enterohepatic Cycling
The hepatic biliary system expels drugs and metabolites via bile secretions.
Hepatocytes lining bile canaliculi produce bile that contains water, ...
Hepatic Drug Excretion: Influencing Factors
Bile, produced by hepatocytes, primarily comprises water, bile salts, and pigments. Membrane transporters in hepatocytes transfer the drug into bile.
...
Drug Excretion: Pulmonary and Glandular Routes
Drugs are excreted through various unconventional routes, including the lungs, breast milk, and saliva.
In the lungs, volatile drugs diffuse into the ...
Drug Excretion: Miscellaneous Routes
Various bodily processes, including sweating, tears, and the digestive system, contribute to drug excretion.
Nonionized lipophilic drugs passively diffuse ...
Drug Clearance: Overview
A drug that enters the body gets eliminated by the kidneys and liver through urine or bile, respectively. A pharmacokinetic parameter, drug clearance, ...
Clearance Models: Physiological Models
Drug clearance features irreversible drug removal from any organ in the body.
Physiological models determine clearance through an individual organ, ...
Clearance Models: Compartment Models
Clearance directly measures drug elimination from the central compartment, which comprises plasma and highly perfused organs like kidneys and liver.
...
Clearance Models: Noncompartmental Models
Typically, clearance describes the drug elimination from the body using compartment models.
An alternative, the noncompartmental approach, estimates ...
Renal Drug Clearance: Overview
Renal clearance is defined as a constant fraction of the central volume of distribution containing the drug excreted by the kidney per unit of time.
It is ...
Renal Drug Clearance: Comparison Between Renal Excretion Methods
Renal clearance is the summation of kidney filtration, secretion, and reabsorption calculated by a specific equation.
It is typically associated with the ...
Factors Affecting Renal Clearance: Drug's Physicochemical Properties and Plasma Levels
Various factors impact a drug's renal clearance, including its physical-chemical properties and plasma levels.
Molecular size, lipid solubility, and ...
Factors Affecting Renal Clearance: Drug Distribution and Drug Interactions
Renal clearance, pivotal in drug elimination, can be affected by drug distribution and interactions.
Drugs with a large distribution volume or bound to ...
Factors Affecting Renal Clearance: Renal Impairment
Renal dysfunction significantly impairs renal drug clearance.
Renal failure can be caused by various factors.
Uremia, characterized by impaired glomerular ...
Renal Failure: Dose Adjustments
In patients with renal impairment, drugs exhibit altered pharmacokinetics.
Reduced renal clearance and elimination rate result in prolonged elimination ...
Determination of Renal Drug Clearance: Graphical and Midpoint Methods
Renal clearance can be determined using graphical and midpoint methods.
In the graphical method, clearance can be calculated and obtained by plotting the ...
Hepatic Drug Clearance: Restrictive and Nonrestrictive Clearance
Hepatic clearance is the volume of blood cleared of a drug by the liver per unit of time. It equals total body clearance minus renal clearance.
Most ...
Hepatic Drug Clearance: Effect of Protein Binding
Hepatic clearance can be affected by protein binding based on the extraction ratio of the drug.
Drugs with high extraction ratios are flow-limited and ...
Hepatic Drug Clearance: Role of Transporters
In the liver's bile canaliculi, modification of influx and efflux transporters can influence intrinsic clearance.
Transporters play a major role in ...
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