Impact of CYP1A2 genetic polymorphisms on pharmacokinetics of antipsychotic drugs: a systematic review and meta‐analysis

• Published in: Acta psychiatrica Scandinavica Vol. 139; no. 1; pp. 15 - 25
• Main Authors: Na Takuathung, M., Hanprasertpong, N., Teekachunhatean, S., Koonrungsesomboon, N.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.01.2019
• Subjects: Adult; Alleles; antipsychotic agents; Antipsychotic Agents - blood; Antipsychotic Agents - pharmacokinetics; Antipsychotics; Clozapine; Clozapine - blood; Clozapine - pharmacokinetics; CYP1A2 protein; Cytochrome P-450 CYP1A2 - genetics; Cytochrome P-450 CYP1A2 - metabolism; Cytochrome P450; cytochrome P‐450 CYP1A2; Drugs; Ethnic Groups - genetics; Ethnic Groups - psychology; Female; Gene polymorphism; genetic; Genotype; Genotyping; Haloperidol; Haloperidol - therapeutic use; Humans; Male; Meta-analysis; Middle Aged; Mutation - genetics; Olanzapine; Olanzapine - blood; Olanzapine - pharmacokinetics; Pharmacokinetics; Polymorphism; Polymorphism, Genetic - genetics; Psychotropic drugs; schizophrenia; Systematic review; genetic; polymorphism; schizophrenia; antipsychotic agents; cytochrome P-450 CYP1A2
• ISSN: 0001-690X; 1600-0447
• DOI: 10.1111/acps.12947

Objective To determine the impact of CYP1A2 genetic polymorphisms on the pharmacokinetics of CYP1A2‐metabolized antipsychotic drugs in humans by means of systematic review and meta‐analysis. Method A systematic search was conducted in PubMed and Scopus databases as of June 26, 2018. Studies reporting the pharmacokinetic parameters of CYP1A2‐metabolized antipsychotic drugs in individuals who were genotyped for CYP1A2 genetic polymorphisms were retrieved. Pharmacokinetic parameters of individuals who have mutant alleles of a CYP1A2 genetic polymorphism were compared with the wild‐type individuals. Pooled‐effect estimates, presented as standardized mean difference, were calculated by means of the fixed‐effect or random‐effects model, as appropriate. Results Ten studies involving 872 clozapine users, seven studies involving 712 olanzapine users, and two studies involving 141 haloperidol users were included. All but one study reported no associations between any CYP1A2 genetic polymorphisms and the pharmacokinetics of CYP1A2‐metabolized antipsychotic drugs. The pooled‐effect estimates through meta‐analyses of seven studies demonstrated no significant associations between the ‐163C>A or ‐2467delT polymorphism and clozapine or olanzapine concentrations in the blood. Conclusions This study suggests that CYP1A2 genetic polymorphisms have no significant impact on the pharmacokinetics of CYP1A2‐metabolized antipsychotic drugs. CYP1A2 genotyping may have no clinical implications for personalized dosing of CYP1A2‐metabolized antipsychotic drugs.