Pampa-d drugs

BALTIMORE, Md.—Before administering new drug candidates to animals or humans to monitor adsorption through cellular membranes, researchers often rely on in vitro tests such as the parallel artificial membrane permeability assay (PAMPA) . But while this assay allows the scientists greater control of conditions over many cell-based assays, there have been few definitive studies of the correlation between permeability and lipid-content. Researchers at the University of Maryland and Gazi University in Ankara, Turkey recently examined this issue more closely, publishing their findings in the European Journal of Pharmaceutical Sciences.

The researchers monitored the behavior of five model compounds in PAMPA experiments of individual phospholipids that varied in phosphate head group and degree of acyl chain saturation. They found that the permeability of some compounds were sensitive to changes in membrane fluidity, which is influenced most directly by variations in phospholipid acyl chains. For example, permeability was lowest membranes of phosphatidylcholines, which offer the most rigid membranes.

Other compounds, however, were sensitive to ion-pair effects promoted by the phosphate head groups and environmental pH. For example, the permeability of metoprolol varied 17-fold under different ionizing conditions. For compounds that generally exhibit poor permeability, changes in membrane fluidity and ionization seemed to have little impact.