Organic cation transporter 2 (OCT2), Multidrug and toxin extrusion protein 1 (MATE1), and Multidrug and toxin extrusion protein 2-K (MATE2-K) (OCTs/MATEs)

The organic cation transporters involved in the renal clearance of paliperidone are a group of membrane proteins that facilitate the active secretion of the drug from the blood into the urine. This system primarily consists of the organic cation transporter 2 (OCT2/SLC22A2), located on the basolateral membrane of renal proximal tubule cells, and the multidrug and toxin extrusion proteins 1 and 2-K (MATE1/SLC47A1 and MATE2-K/SLC47A2), located on the apical membrane [4, 12, 16]. Paliperidone, an atypical antipsychotic, is significantly dependent on renal elimination, with approximately 59% of a dose excreted unchanged in the urine [1, 3]. The coordinated action of these transporters ensures the efficient removal of paliperidone, which exists as a cation at physiological pH [2]. Although clinical studies with inhibitors like trimethoprim have shown that these transporters may not be the sole determinants of paliperidone's pharmacokinetics, they are critical components of its renal disposition [2, 6]. In patients with renal impairment, the reduced activity of these transporters leads to decreased clearance and increased systemic exposure, necessitating dose adjustments to avoid toxicity [3, 8]. Furthermore, interactions with other drugs that inhibit or compete for these transporters can potentially alter paliperidone levels, although such effects are often secondary to the influence of P-glycoprotein (P-gp), which also contributes to its renal secretion [7, 19]. Understanding the role of these transporters is vital for clinicians to manage the risk of dose-dependent adverse effects such as extrapyramidal symptoms and prolactin elevation [3, 10]. Overall, the OCT/MATE system is a key determinant of the safety and efficacy profile of paliperidone in diverse patient populations [15, 17].

Other names

SLC22A2SLC47A1SLC47A2Solute carrier family 22 member 2Solute carrier family 47 member 1Solute carrier family 47 member 2Multidrug and toxin extrusion protein 1Multidrug and toxin extrusion protein 2-KOCT2MATE1MATE2-K

Active tubular secretion of organic cations via basolateral uptake and apical efflux