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 ABCB1_wt and ABCB1_1199A recombinant cell models were constructed to study the sensitivity, intracellular accumulation, and transepithelial permeability of antipsychotic drugs. ABCB1_1199A 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 ABCB1_wt 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 ABCB1_1199A recombinant cells was greatly decreased compared to ABCB1_wt 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 ABCB1_1199A recombinant cells compared with ABCB1_wt 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.