Effect of CYP2D6 and ABCB1 polymorphisms on pharmacokinetics and efficacy of aripiprazole in pediatric tic disorders

Abstract Backgrounds: Aripiprazole(ARI) is the first-line treatment for tic disorders (TD). It is metabolized by cytochrome P450(CYP)2D6(CYP2D6) and ATP‐binding cassette, sub-family B, member 1(ABCB1) genes. However, whether the clinical efficacy/pharmacokinetics of ARI will be influenced by genetic polymorphisms is not clear. Methods: CYP2D6 and ABCB1 genotyping was performed. The pharmacokinetic parameters of ARI and DARI were obtained by the population pharmacokinetic model established previously. Drug response after ARI administration was evaluated according to reduction rate of Yale Global Tic Severity Scale score. Results: The DARI/ARI metabolic ratios(MRs) of AUC0-t, Cmin and Cmax at the steady state were significantly associated with polymorphisms of rs1135840, rs5030865, rs1058164, rs28371702, rs1065852, rs1080989. The clearance(CL) of ARI were influenced by rs1135840, rs5030865, rs1080989. Rs16947, rs29001518, rs1080985 were correlated with CL of DARI. CYP2D6 polymorphisms(rs5030865) variant was associated with volume of distribution(V) of DARI. ABCB1(C3435T) rs1045642 influenced V or ARI. Rs1065852, rs1080989 was significantly associated with drug response of ARI in children with TD. Conclusion: Clinical efficacy of TD was related with polymorphisms of rs1065852, rs1080989 and CYP2D6 genotyping was recommended in ARI treatment. More evidence and researches are needed to support the role of ABCB1 SNPs in ARI metabolization.