the rate of drug transformation. People who are slow metabolizers may experience toxicity from a drug at doses considered therapeutic. Conversely, rapid metabolizers require more drug to reach therapeutic levels in blood.
Excretion
Drugs and their metabolites are primarily excreted by two routes: (i) glomerular filtration into urine and (ii) transport into bile.
The kidneys remove most drugs and their metabolites from the body. The pH of the glomerular filtrate affects the excretion of weakly acidic and basic drugs, because ionized molecules are not reabsorbed by renal tubules. Molecules that are smaller and more water soluble are usually excreted in this way.
Biliary excretion requires active transport of drugs and metabolites out of liver cells and into the biliary system. Bile flows into the duodenum, and its contents are ultimately discharged in feces. Drugs that are larger (molecular weight [MW] >300) and more lipophilic are preferentially excreted in bile.
Other routes of excretion exist but are less important. Volatile compounds can diffuse out of capillaries in the alveolar wall and enter the air spaces of the lungs, from which they are exhaled (e.g., ethanol). Excretion of drugs in breast milk may affect infants who are breastfeeding.
Disease of the kidneys or liver can impair excretion, causing drug levels in blood and other body fluids to rise.
Further Reading
Book chapter
1 Correia, M.A. (2012). Drug biotransformation. In: Basic and Clinical Pharmacology, 12e (eds. B.G. Katzung, S.B. Masters and A.J. Trevor), 53–68. New York: McGraw‐Hill.
Websites
Pharmacology Education Project
www.pharmacologyeducation.org/clinical‐pharmacology/clinical‐pharmacokinetics
MSD Manual
Drug Absorption
www.msdmanuals.com/professional/clinical‐pharmacology/pharmacokinetics/drug‐absorption
Drug Bioavailability
www.msdmanuals.com/professional/clinical‐pharmacology/pharmacokinetics/drug‐bioavailability
Drug Distribution to Tissues
www.msdmanuals.com/professional/clinical‐pharmacology/pharmacokinetics/drug‐distribution‐to‐tissues
Drug Metabolism
www.msdmanuals.com/professional/clinical‐pharmacology/pharmacokinetics/drug‐metabolism
Drug Excretion
www.msdmanuals.com/professional/clinical‐pharmacology/pharmacokinetics/drug‐excretion
Videos
Pharmacokinetics 1 – Introduction
www.youtube.com/watch?v=8‐Qtd6RhfVA
Pharmacokinetics 2 – Absorption
www.youtube.com/watch?v=pWW‐aq7iSa0
Pharmacokinetics 3 – Distribution
www.youtube.com/watch?v=6erefsWCVxg
Pharmacokinetics 4 – Metabolism
www.youtube.com/watch?v=ztsBn8gsfHw
Pharmacokinetics 5 – Excretion
www.youtube.com/watch?v=VZRVt9r4oSM
3 Specimen Collection
Testing for drugs and toxins can be performed on a variety of specimens. Choosing the most appropriate one depends on the purpose of the analysis.
Types of Specimens
Blood
Blood is the specimen of choice for assessing the amount of active drug in a patient. This information is required in a number of situations, such as:
monitoring the concentration of a prescribed drug to ensure therapeutic levels are present (eg, carbamazepine in a patient with epilepsy)
measuring the amount of a potentially toxic drug to guide therapy and assess prognosis (eg, acetaminophen in a patient who took an overdose)
identifying a cause for altered mental status (eg, ethanol in a comatose patient).
In most cases, drugs are measured in serum. Whole blood is required for certain analyses, because the drug or toxin of interest accumulates within red blood cells.
Collecting blood is an invasive procedure – inserting a needle through skin into a vein – and it causes anxiety and discomfort to some patients. Experienced phlebotomists can draw blood with little or no associated pain, and they ensure that the sample is from the person on whom it was ordered.
Urine
Urine is the best sample for determining whether someone has taken a drug within the recent past. It is an aqueous fluid that contains both drugs and their metabolites in a concentrated form. The window of detection varies from hours to a week or longer, depending on
