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The page below is a sample from the LabCE course Drug Metabolism. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Elimination, continued

Weak acid drugs
When the pH of the urine is above the drug’s pKa,
  • more drug will be present in the ionized form.
  • the ionized form is more polar and, thus, more soluble in water.
  • the ionized form does not cross cell membranes easily.
  • more drug will be excreted.
  • this results in a decreased amount of time in which the drug can be detected (decreased window of detection).
When the pH of the urine is below the drug’s pKa,
  • more drug will be present in the unionized form.
  • the unionized form is less polar and, thus, less soluble in water.
  • the unionized form crosses cell membranes easily.
  • more drug will be reabsorbed.
  • this results in an increased amount of time in which the drug can be detected (increased window of detection).
Weak base drugs
When the pH of the urine is above the drug’s pKa,
  • more drug will be present in the unionized form.
  • the unionized form is less polar and, thus, less soluble in water.
  • the unionized form crosses cell membranes easily.
  • more drug will be reabsorbed.
  • this results in an increased amount of time in which the drug can be detected (increased window of detection).
When the pH of the urine is below the drug’s pKa,
  • more drug will be present in the ionized form.
  • the ionized form is more polar and,thus, more soluble in water.
  • the ionized form does not cross cell membranes easily.
  • more drug will be excreted.
  • this results in a decreased amount of time in which the drug can be detected (decreased window of detection).
Some drug metabolites produced in the liver are excreted into the intestines through the bile. Whether a drug is excreted in bile or urine depends on its molecular weight and the polarity of the metabolite. Compounds with large molecular weights and low water solubility are more likely secreted in bile. THC is an example of a metabolite that is secreted into the bile and then into the intestines. About 55% of THC is secreted in the feces with about 20% in the urine.