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Purpose  Polymeric drugs, including patiromer (Veltassa®), bind target molecules or ions in the gut, allowing fecal elimination. Non-absorbed insoluble polymers, like patiromer, avoid common systemic drug-drug interactions (DDIs). However, the potential for DDI via polymer binding to orally administered drugs during transit of the gastrointestinal tract remains. Here we elucidate the properties correlated with drug-patiromer binding using quantitative structure-property relationship (QSPR) models.    Methods  We selected 28 drugs to evaluate for binding to patiromer  in vitro  over a range of pH and ionic conditions intended to mimic the gut environment. Using this  in vitro  data, we developed QSPR models using step-wise linear regression and analyzed over 100 physiochemical drug descriptors.    Results  Four descriptors emerged that account for ~70% of patiromer-drug binding  in vitro : the computed surface area of hydrogen bond accepting atoms, ionization potential, electron affinity, and lipophilicity ( R   2   = 0.7,  Q   2   = 0.6). Further, certain molecular properties are shared by nonbinding, weak, or strong binding compounds.    Conclusions  These findings offer insight into drivers of  in vitro  binding to patiromer and describe a useful approach for assessing potential drug-binding risk of investigational polymeric drugs.    Electronic supplementary material  The online version of this article (10.1007/s11095-018-2356-y) contains supplementary material, which is available to authorized users.

Use of QSPR Modeling to Characterize In Vitro Binding of Drugs to a Gut-Restricted Polymer