Lecture 8 Absorption Mechanisms

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11 Apr 2012

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Lecture 8 PCL201
Passive Diffusion of Water Soluble Compounds
Aquaporin channels
Most allow only water but A-3 allows small water soluble molecules
Pore width ~8-10 Angstroms, therefore allows hydrophilic molecules <200Da
Only Small molecules
High concentration to low concentration via passive diffusion
Remember Compounds that are hydrophilic have low Pow
Increased molecular size, decreased permeation rate (ability of molecule to cross
Passive Diffusion: Lipid Soluble Compounds
Lipid soluble drugs diffuse across lipid molecules of membrane
Rate of diffusion depends on
Concentration of drug
Degree of ionization
Surface area of membrane (stomach vs. small intestine)
Concentration of drug and the diffusion across the membrane is not always linear
Major issue with regulating drug dosage
Can not always assume linear relationship
Role of Pow – partition coefficient major factor with regards to drug absorption
Ideally the higher Pow the more rapidly absorbed
Review: Optimum value for drug abosprtion due to hydrophilic barrier associated with
glycocalyx: cut off phenomenon
Very lipophillicreduced absorptionunable to cross stagnant water layer
Increased Pow, increased absorption rate until reaching the cut-off value, where
there is reduced permeability.
Degree of ionization: pH and protonation
Charged molecules vs. uncharged molecules
The pH of compartment and pKa of drug.
Surface Area: more area available for diffusion, the more diffusion can occur
Increased surface area, available for lipophillic compounds to cross
Rate of drug absorption related to rate of stomach emptying.
With fooddelay
With waterreduce delay
Facilitated Diffusion
Via carrier molecules
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