Figure 3.

(a) Matrix approach for hepatic organic anion‐transporting polypeptides (OATPs). Three key OATPs, OATP1B1, OATP1B3, and OATP2B1, are expressed within the healthy liver of adults. Because there is a significant overlap in probe selectivity for OATPs and highly potent and selective probes are currently unknown for any specific OATP, a matrix approach is proposed. For the compounds in the box to the left, physiologically‐based pharmacokinetic (PBPK) models have been published for these substrates of OATPs, but all models are fit‐for‐purpose models using a lumped clearance for OATPs. For more mechanistic understanding of hepatic OATPs, kinetics for the transporters, and it should be included into the model as done for the compounds listed as “substrates.” The dotted line indicates that the clinical drug‐drug interaction (DDI) is not available for verification. (b) Matrix approach for renal organic anion transporters (OATs). Three OATs, OAT1, OAT3, and OAT4, are expressed within the healthy kidney of adults. Because there is a significant overlap in probe selectivity for OATs and highly potent and selective probes are currently unknown for any specific OAT, a matrix approach is proposed. For the compounds in the box to the left, PBPK models have been published for these substrates of OATs, but all models are fit‐for‐purpose models using a lumped clearance for OATs. For more mechanistic understanding of renal transporter‐mediated DDIs, kinetics for the transporters, and it should be included into the model as done for the compounds listed as “substrates." The dotted line indicates that the clinical DDI is not available for verification. BCRP, breast cancer resistance protein; MATE, multidrug and toxin extrusion; P‐gp, P‐glycoprotein. [Colour figure can be viewed at http://www.wileyonlinelibrary.com]