Absorption, Distribution

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• Absorption, Distribution Biotransformation
• Absorption Distribution
• Anatomy of Cell Membrane (solubility, ionization)
• Absorption (GI tract, lungs, skin)
• Distribution
• Plasma-protein transport
• Blood-brain barrier
• Storage
• Tissue-plasma equilibrium

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Local effects vs Systemic effects
Requires absorption Where?? How??
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Anatomy of Cell Membrane
a. Protein channels b. Phospholipid
bilayer Selectively permeable

• Polarity/solubility
• pH an Ionization
• Carboxylic acid
• Strychnine
• 2,4,D
• Concentration Depnt.
• Carrier-mediated transport

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Quiz Which chemicals are most water soluble?
Which are least water soluble? Why?
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Ionization
Carboxylic acid (COOH) Strychnine 2,4 D
(herbicide)
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Ionization and Diffusion Across a Membrane
Stomach (pH 2.0)
Blood (pH 7.2)
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Ionization and Diffusion Stomach vs Intestine
Stomach
Weak acid
Note magnitude of equilibrium arrows
Weak base
Intestine
Weak acid
Weak base
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• Respiratory absorption
• Lung surface area 100 m2
• Dermal absorption

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Distribution
1. Plasma transport (non-covalent, covalent
binding to proteins
Non-polar
Polar
Non-Polar
Polar
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• 2. Blood-brain barrier placental barrier
• 3. Storage
• Kidney liver (metallothioneins)
• Fat (eg. PCBs)
• Bone (eg. lead, fluoride)
• Hair, fingernails (eg. arsenic)
• 4. Tissue-plasma equilibrium

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Excretion

• Kidneys (most small MW, polar)
• Gall bladder (larger MW polar conjugates)
• Faeces
• Biliary excretion

• Lungs, skin, sweat, milk

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M.W.
Kidneys
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Effect of Bile Duct Ligation/Blockage
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