ChemCases.Com
Drug Pathways and Chemical Concepts

Prof. Sally Boudinot

Please remember these concepts:

1. Many processes can be at equilibrium.   But with changes in condition - concentration, temperature -  the system will no longer be at equilibrium and will adjust to try to get there again.
2. The equilibrium concentrations of H₃O⁺ and OH^- are vanishingly small in pure water. 
3. A weak acid or a weak base drug, in water, will disassociate to some extent.  The pH of the drug solution  will depend upon the pK_a.
4. Buffers stabilize pH.  This stabilized acidity determines the form of drug disassociation in systems.  The Henderson-Hasselbach equation conveniently handles drug ionization questions for buffered systems like the body.

The stomach: Taking an average pH value of 2:
	From these calculations, we can easily see that the unionized form of phenobarbitol predominates in regions of low pH, or high acidity. From using the Henderson-Hasselbach equation, we can see that for every ionized phenobarbitol molecule in solution, there are nearly 260,000 molecules of the unionized species available to cross the lipid stomach membrane.  But the surface area for absorption is small and the transit time of contents within the stomach is very short, and most of these unionized phenobarbitol molecules are  transported farther down the alimentary canal before they are absorbed.
We can easily calculate the percent of ionized and unionized molecules in the solution at a given pH.	Ionized (Dissociated) vs. Unionized Phenobarbitol Location/pH Stomach/pH=2 Duodenum/pH=6 Jejunum/pH=7.5 Blood/pH=7.4 Unionized (%) 99.999       Ionized(%) 4x10-4

to Ionization within the Duodenum

Principal Investigator
Laurence I. Peterson, Dean
College of Science and Mathematics
Kennesaw State University
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Kennesaw, GA 30144-5591
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email lpeterso@kennesaw.edu

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Beaufort, SC 29907
843-322-0486

email hayden@islc.net