The Substrate Specificity of OATPsOatps

OATP/Oatp family members mediate transmembrane transport of a wide range of organic compounds (Table 7.7) (Hagenbuch and Meier, 2003; Tirona and Kim, 2002; Koepsell and Endou, 2004; Sai and Tsuji, 2004) including (1) organic anions, such as bromosulfophthalein (BSP), bile salts, bilirubin, prostaglandins, and estrogen-conjugates; (2) neural steroids and steroid conjugates; (3) lipophilic organic cations, e.g., rocuronium; and (4) organic dyes, thyroid hormones, and anionic oligopeptides. Various pharmaceutically relevant compounds such as digoxin, pravastatin, methotrexate, temocaprilat, benzylpenicillin, fexofenadine, (D-Pen2, D-Pen5)-enkephalin (DPDPE), as well as some NSAIDs are also substrates of OATP/Oatp isoforms (Hagenbuch and Meier, 2003; Tirona and Kim, 2002; Koepsell and Endou, 2004; Sai and Tsuji, 2004) (Table 7.7). The clinical significance of the OATP/Oatp family is readily apparent given the wide range of pharmaceutical substrates for its members. The tissue expression patterns and cellular localization of OATP/Oatp isoforms (see below), make these transporters attractive targets to enhance drug bioavailability.

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