Drug pathways and Chemical Concepts - 14c Absorption in the Jejunum and Ileum

14c. Anatomy of the Gastrointestinal Tract and Phenobarbitol Absorption

Please remember these concepts:

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.
The equilibrium concentrations of H₃O⁺ and OH^- are vanishingly small in pure water.
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.
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.

Further along the small intestine (jejunum and ileum), the pH rises and averages 7.5:

Taking an average pH value of 7.5,
we can again calculate the ratio of the species:

We can easily calculate the percent of ionized and unionized molecules in the solution at this pH.
The result of this calculation shows us that disassociated phenobarbitol is slightly favored. Thus, the concentration of absorbable, unionized phenobarbitol is about one half than that further up in the duodenum. Nevertheless, the drug is primarily in the unionized form but the absorption of phenobarbitol is slower in this section of the GI tract because the surface area of this portion of the tract is lower.

Ionized (Dissociated) vs. Unionized Phenobarbitol

Location/pH	Stomach/pH=2	Duodenum/pH=6	Jejunum/pH=7.5	Blood/pH=7.4
Unionized (%)	99.999	96.3	55
Ionized(%)	4x10^-4	3.7	45

to Ionization in the Blood

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