The possible clinical impact of risperidone on P ‐glycoprotein‐mediated transport of tacrolimus: A case report and in vitro study

Abstract The authors encountered the case of an 8‐fold increase in the concentration/dose (C/D) ratio of tacrolimus (TAC) following the coadministration of voriconazole (VRCZ) in a hematopoietic stem cell transplantation (HSCT) recipient. The interaction observed was much greater than expected and the patient had also been treated with oral risperidone (RSP). We hypothesized that cytochrome P450 (CYP)3A inhibition of the small intestine by VRCZ and P‐glycoprotein (P‐gp) inhibition of the small intestine by RSP exerted a synergistic effect on the bioavailability of TAC. The aim of the present study was to evaluate the effect of RSP on the P‐gp‐mediated transport of TAC. Transcellular transport of P‐gp substrates was examined in Caco‐2 and P‐gp‐expressing renal epithelial LLC‐GA5‐COL150 cells. In Caco‐2 cells, the apical‐basal (A‐B) transport of rhodamine123 (Rh123) after 120‐min incubation was increased by 47.1%, whereas that in the B‐A direction was decreased by 61.7% in the presence of RSP (100 μM). These results indicate that RSP showed an inhibitory effect on the P‐gp‐mediated transport of Rh123. In LLC‐GA5‐COL150 cells, the A‐B transport of TAC after 120‐min incubation was increased by 21.7% in the presence of RSP (100 μM), whereas that in the B‐A direction was decreased by 10.7%. These results suggest that RSP was at least partly involved in the mechanism of the marked increase in the C/D ratio of TAC. This case report prov...
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL PAPER Source Type: research