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pH Partition Theory

Exam 6- Dr. Mahato
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pH Partition Theory
Drugs are absorbed from the biological membranes by passive diffusion depending on the fraction of un-ionized form of the drug at the pH of that biological membrane.
Degree of Ionization
Depends on both their pKa and the solution pH.
Ionized drugs are more hydrophilic and have minimal membrane transport compared to the un-ionized form of the drug.
Solution pH will affect the overall partition coefficient of an ionizable substance.
pKa
The pKa of the molecule is the pH at which there is a 50:50 mixture of conjugate acid-base forms.
The conjugate acid will predominate at a pH lower than the pKa and the conjugate base form will be present at a pH higher than the pKa.
Limitations of pH Partition Theory
pH partition theory often doesn't hold true for most weak acids, which are well absorbed from the small intestine.
Quaternary ammonium compounds are ionized at all pH's but are readily absorbed from the GI tract.
pH Partition Theory dose not take Account the following:
Large epithelial surface areas of small intestine compensates for ionization effects.
Long residence time in small intestine compensates for ionization effects.
Charged drugs, such as quaternary ammonium compounds and tetracyclines, may interact with opposite charged organic ions, resulting in a neutral species, which are absorbable.
Some drugs are absorbed by active pathways and many more.
Drug absorption is also affected by its lipid solubility.
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