ABCB1 1199G > A Polymorphism Impacts Transport Ability of P-gp-Mediated Antipsychotics.

The alterations in P-glycoprotein (P-gp)-mediated transport of antipsychotics due to the ABCB1 1199G>A polymorphism were assessed in the current study. The ABCB1wt and ABCB11199A recombinant cell models were constructed to study the sensitivity, intracellular accumulation, and transepithelial permeability of antipsychotic drugs. ABCB11199A recombinant cells had more sensitivity to olanzapine (2.2-fold, p < 0.01), aripiprazole (1.8-fold, p < 0.01), amisulpride (2.3-fold, p < 0.01), and risperidone (3.1-fold, p < 0.01) than ABCB1wt cells, while the resistance to paliperidone in both recombinant cell models was similar. In addition, the uptake quality of olanzapine, aripiprazole, amisulpride, and risperidone in ABCB11199A recombinant cells was greatly decreased compared to ABCB1wt cells (3.2-fold, p < 0.01; 3.7-fold, p < 0.01; 3.1-fold, p < 0.01; 2.6-fold, and p < 0.01, respectively). Furthermore, apparent permeability values were greatly increased in ABCB11199A recombinant cells compared with ABCB1wt recombinant cells for olanzapine (2.7-fold, p < 0.01), aripiprazole (2.9-fold, p < 0.01), amisulpride (3.4-fold, p < 0.01), and risperidone (4.1-fold, p < 0.01). The influence of ABCB1 1199G>A polymorphism on the transport of P-gp-mediated substrates showed up as drug-specific. Collectively, the ABCB1 1199G>A polymorphism may impact effective antipsychotics concentration in target cells via mediating the agents transport and distribution.