The Effect of Molecular Structure on the

Bioavailability of Pharmaceuticals
Jenny Van, Cindy Xu, Karen Zhang
University of Washington Department of Chemistry
Faculty Advisor: Dr. Brandi Cossairt

Introduction
The focus of our research is on analyzing molecular structure factors that affect oral
Factors Affecting Bioavailability Challenges in the Field of Bioavailability
bioavailability, which include rotatable bonds, polar surface area, electron affinity,
and aromaticity. We also consider current challenges in the field of bioavailability
and possible solutions to those challenges. Dielectric Effect Electron Affinity Polar Surface Area Aromaticity

Fig. 7. The intravenous route is set at 100%

bioavailability because the drug is injected directly
into the circulatory system. Oral bioavailability by
contrast is much lower because the drug has to
pass through the GI tract to reach the circulatory
system. The y-axis represents the drug’s Fig. 10. Electron affinity
Fig. 9. Polarized
concentration (mg/L). As concentration increases, vs. atomic number
atom
the rate of drug entering the system is greater than
the rate in which it exits and vice versa. Fig. 11. CHF3 Fig. 12. Benzene
Fig. 5. Molecular weight distribution for the 277-compound Goodman and Gilman
human oral bioavailability data set (left) and 1117-compound proprietary rat oral
bioavailability set (right).

Background Info on Drug Absorption

Fig. 3. From left to right, effect that dielectric capacity, electron affinity, polar surface
area, and aromaticity have on percent bioavailability.

Rotatable Bond Count

Fig. 6. Lipinski’s Rule of Five is used to identify orally active drugs.

Fig. 1-2. The longer the drug stays in the small intestine, which is the main location of
drug absorption, the greater its total absorption will be. Drugs are carried from the
blood supply directly to the liver through the portal vein when they reach the blood
vessels of the gastrointestinal tract. The liver is the main source of enzymes that
breaks down the drugs, so they must avoid being metabolized by those enzymes in
order to reach the circulatory system. Drugs that end up in blood vessels have to then
be absorbed from those vessels via diffusion in order to reach their target site.
Fig. 3. The drug is absorbed across the
membrane of the stomach and intestines,
which is made of phospholipids. The drug
has to be soluble in lipids in order to be
able to pass through the membrane.
Molecules that are small and nonpolar are
lipophilic, while large charged molecules
are not.
Fig. 13. Rotatable bonds in a molecule
Other factors that affect bioavailability:
References
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