Drug Pathways and Chemical Concepts - 14b Absorption in the Duodenum

14b. 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.

In the duodenum (the first segment of the small intestines) the pH is approximately 6

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This gives us the ratio of ionized to unionized phenobarbitol in solution in the duodenum.

We can see that as in the stomach, there exists a preponderance of unionized molecules available for absorption. The large surface area of the small intestine provides a favorable environment for absorption to take place.

As phenobarbitol is transported through the duodenum, the unionized drug is available to cross the lipid membranes for absorption.

Unionized phenobarbitol is continuously resupplied by the efforts of the system to reach equilibrium. As each unionized molecule crosses the membrane, it is removed from the gastrointestinal tract, shifting the equilibrium to favor the acceptance of a proton from a molecule of the ionized species:

A^- + H₃O⁺ <===> HA + H₂O

Again, it might be useful to calculate the percent of each species.

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
Ionized(%)	4x10^-4	3.7

to Absorption in the Jejunum and Ileum

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