A novel study led by Per Artursson (Uppsala University/SciLifeLab) demonstrates that phospholipid content within cells is a major determinant for how large portion of an administered drug that is available to exert its action. It also suggests pure phospholipid beads as a cell-free alternative for assessing drug binding in cells. The results are published in Molecular Pharmaceutics.
The intracellular concentrations of drugs are rarely equivalent to those detected in blood. Several structures of cell interiors can bind drug molecules and thereby lower the pharmacologically relevant concentrations. Evaluating this bioavailability parameter is an important step in any drug development process, to improve prediction of drug efficacy and toxicity.
Experiments exposing phospholipid-rich cells to 23 different drug compounds now establish that higher phospholipid content led to higher intracellular drug binding and a lower intracellular bioavailability.The current study also reveal a good correlation between drug binding to beads coated with pure phospholipids and intracellular drug binding, proposing this as an easier alternative to cell-based techniques.