Polymorphic transporters and platinum pharmacodynamics

Abstract

Several solute carriers and ATP-binding cassette transporters have been implicated in the influx or efflux of platinum-based chemotherapeutic agents such as cisplatin, carboplatin, and oxaliplatin. Given that many of these proteins are highly polymorphic, the genetic status of these proteins could be an important contributor to the extensive interindividual pharmacokinetic variability associated with the clinical use of these agents. In this review article, we provide an updated overview of the various transporters that have shown promise in animal models or patient populations in facilitating the movement of platinum-based agents across cell membranes, and how their function is associated with drug disposition or pharmacodynamic effects.

Fig. 1

Chemical structures of cisplatin (A), carboplatin (B), oxaliplatin (C), nedaplatin (D) and picoplatin (E).

Fig 2

Transporters involved in the uptake or elimination of platinum-based chemotherapeutic agents in human liver (A), kidney (B), or tumor (C). Arrows depict the direction in which transport occurs at the basolateral (BM), canalicular (CM) or apical membrane (AM).