A research group at Sweden’s Uppsala University has presented its findings in scientific journal Proceedings of the National Academy of Sciences(PNAS), explaining the method determines a drug’s bioavailability – the measurement of the rate and extent to which a drug is made available to the site of action - inside cultured cells.
The ‘short-cut’ method
The method, which Uppsala University professor Per Artursson said can be adopted to any cell type of interest, addresses how drugs partly ‘disappear’ in cells.
“By measuring the unbound quantity of the drug in the cells, the method takes into account how the drug partly ‘disappears’ when it binds to various cell components where it cannot exert its intended effect.”
“This ‘disappearing’ proportion of the drug varies from one molecule to another and has hitherto been hard to predict, but can now be easily determined with the researchers’ small-scale method,” said the University.
Despite the method’s advantages, Artursson said equipment cost may limit its adoption in the pharmaceutical industry.
“The method does require state of the art mass spectrometry equipment, which can be a drawback for smaller companies,” he said.
Artursson told us the method could become the industry standard.
“Today, the industry often uses an assay, where the transport across a cell monolayer (grown on permeable supports) is determined. This assay was developed by us many years ago for prediction of intestinal permeability across cells and hence drug absorption after oral administration, but it is often extrapolated by the industry to predict uptake of a drug into cells.”
“We show in [the PNAS] paper that intracellular bioavailability is not correlated to permeability across cells.”
“Therefore, our new assay has the potential to become a new standard for such measurements. In fact, several big pharma are already implementing the method,” he said.
The researchers say the method may also be used to improve target exposure in medicine design.
“Our approach is generally applicable to multiple targets, cell types, and therapeutic areas. We expect that routine measurements of intracellular drug concentration will contribute to the design and selection of medicines with improved target exposure, reducing the high attrition observed in drug development.”
“The technology is also useful in the prediction of drug metabolism and clinical drug-drug interactions,” he said.
The technology is currently available at SciLifeLab in Uppsala.