Extent of Absorption

• Incomplete absorption following oral drug administration is common:

  • For example,nly 70% of a digoxin dose reaches systemic circulation. Factors:

    • Poor GI tract absorption

    • Digoxin (Lanoxin, Lanoxicaps):  metabolism by gastrointestinal flora

• Very hydrophilic drugs - not be well absorbed --cannot cross cell membrane lipid component

• Excessively lipid-soluble (hydrophobic) drugs may not be soluble enough to cross a water layer near the cell membrane.

Ion Trapping

• Kidney:

  • Nearly all drugs filtered at the glomerulus:

    • Most drugs in a lipid-soluble form will be reabsorbed by passive diffusion.

    • To increase excretion: change the urinary pH to favor the charged form of the drug since charged form cannot be readily reabsorbed (they cannot readily pass through biological membranes)

      • Weak acids: excreted faster in alkaline pH (anion form favored)

      • Weak bases: excreted faster in acidic pH (cation form favored)

• Other sites:

  • Body fluids where pH differences from blood pH favor trapping or reabsorption:

    • Stomach contents

    • Small intestine

    • Breast milk

    • Aqueous humor (eye)

    • Vaginal secretions

    • Prostatic secretions

Weak bases-- amines

•  N + 1 carbon (R) and 2 hydrogens: primary amine (reversible protonation)

•  N + 2 carbons (R) and 1 hydrogen: secondary amine (reversible protonation)

•  N + 3 carbons (R): tertiary amine (reversible protonation)

•  N + 4 carbons (R): quaternary amine (permanently charged)