The results indicate unexpected and previously unknown drug-membrane interactions that can have far-reaching consequences for the pharmacokinetics of commonly prescribed drugs in polypharmacy patients. As both permeability and the membrane partitioning coefficient can be upregulated or downregulated several times in a manner that is difficult to predict simply from the molecular properties, this work highlights the need for a systematic screening of currently prescribed drugs for interactions at the permeation and biodistribution level, rather than at the metabolic level. The knowledge obtained in such co-permeation screening should then lead to better informed prescription and dosage decisions by physicians who so-far rely solely on single-molecule data.