Drug makers might be able to triple the absorbing power of some medications and lower toxic risks of others, as a result of a study at the University of Maryland, Baltimore on how bile acids travel through the gut.
The study, by Peter Swaan, PhD, professor, and colleagues at the Maryland School of Pharmacy, has been boosted by a $1.5 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases.
Swaan says the researchers want to exploit the natural cleansing and digesting process of bile acid recycling through the gall bladder, intestines, and liver. By studying the structures of intestinal bile acid transporters, special membrane embedded proteins that ease bile acids through, perhaps drugs can be designed to better transport through intestinal membranes, which are highly complex, he says.
Swaan says that prior to the new grant, "We have made some fairly good progress. This builds on our previous work that helped us find key residues for apical bile salt [acid] transporters that play a role in drug-protein interactions. We can develop a three-dimensional model, which can be used in the rational design of novel therapeutics …. for enhanced intestinal permeability."
Many medication compounds and nutrients can get stuck in membranes in the intestine. Bile acid transporter proteins help them along. "We can determine how the compounds travel across the membrane," Swaan adds.
Also, the study could help lower doses of drugs already on the market to make them safer and still effective and lower toxicity risks in some patients. The study could also help some drugs in manufacturers' pipelines absorb better. About half of all drugs that are tested in clinical trials fail due to inadequate absorption into the body. The study could result in more drug candidates reaching market, says Swaan.