An Introduction to Testing for Drugs of Abuse. William E. Schreiber

Figure 2.1 Structures of uridine diphosphate (UDP) glucuronic acid and phosphoadenosine phosphosulfate (PAPS), which serve as donors for glucuronic acid and sulfate in phase II reactions. The glucuronic acid and sulfate groups are indicated by rectangles. Addition of either group to a drug molecule increases its water solubility and facilitates excretion in urine and/or bile.

      The rate of metabolism varies among individuals. Genetic polymorphisms in CYP and other drug‐metabolizing enzymes affect their activity and can accelerate or slow down 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

      Websites

      Pharmacology Education Project

      MSD Manual

      Drug Absorption

      Drug Bioavailability

      Drug Distribution to Tissues

      Drug Metabolism

      Drug Excretion

      Videos

      Pharmacokinetics 1 – Introduction

      Pharmacokinetics 2 – Absorption

      Pharmacokinetics 3 – Distribution

      Pharmacokinetics 4 – Metabolism

      Pharmacokinetics 5 – Excretion