Influence of CYP2D6 gene polymorphisms on the pharmacokinetics of aripiprazole in healthy Chinese subjects

Background: Pharmacogenetics study was added into 2 bioequivalence trials of aripiprazole. The correlation between CYP2D6 polymorphisms and aripiprazole pharmacokinetics (PK) was analyzed. Materials & methods: A total of 140 subjects were included. A total of 26 CYP2D6 gene alleles were detected. The plasma concentration of aripiprazole was measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). SPSS Statistics 21 was used to analyze the correlation between CYP2D6 polymorphisms and aripiprazole PK parameters. Results: All of the four PK parameters were significantly influenced by CYP2D6 rs1058164 and rs28371699. t1/2 and area under the concentration-time curve (AUC0–∞) exhibited significant difference between CYP2D6 extensive metabolizers and intermediate metabolizers. Conclusion: Aripiprazole PK was greatly influenced by CYP2D6. Attention should be paid to the possible dose adjustment for CYP2D6 intermediate metabolizer population when the drug is used in Chinese patients.

High prevalence of CYP2D6 ultrarapid metabolizers in a mestizo Colombian population in relation to Hispanic mestizo populations

Background: Interethnic differences in CYP2D6 allele frequency have been demonstrated across Latin–American countries. Only one previous study describing CYP2D6 genotypes in Colombian population has been performed. Thus, this study aimed to evaluate the CYP2D6 genetic variability in a mestizo Colombian population, as well as the similarities and differences concerning other Hispanic mestizo (HM) populations. Methodology: Two hundred and twelve unrelated healthy Colombian subjects were studied, in which different CYP2D6 polymorphisms were analyzed by extra long-PCR and real-time PCR. Results & discussion: A high percentage of ultrarapid metabolizers (18.4%) was found, representing the highest frequency calculated within the HM populations studied. However, the percentage of poor metabolizers (4.7%) was similar to those previously reported in HM populations.

Genetic Polymorphisms of CYP2D6: Prevalence in Healthy Kurds

Background: Identifying the genetic polymorphisms of drug metabolizing enzyme CYP2D6 is useful in pharmacogenomics. Unfortunately, until today, the prevalence of the CYP2D6 polymorphisms among Kurds is scarce. Objective: In this study, we explored the CYP2D6 polymorphisms among Kurds. Methods: Four hundred and fifty-nine unrelated healthy Kurds were recruited for the study. DNA was extracted from whole blood and was then used for genotyping CYP2D6*3, *4, *5, *6, *9, *10, *17, *114 and gene duplication using the nested allelespecific multiplex Polymerase Chain Reaction (PCR). Conclusion: The data add to our knowledge of CYP2D6 alleles, the genotypes and the distributions of predicted phenotypes in Kurds. Majority of the observed variant alleles confer no function and gene duplication. CYP2D6 polymorphisms were found to be very heterogeneous in relation to genotype frequencies. Further study in relation to the evaluation of drug therapy adjustment based on CYP2D6 genotype may help to understand the clinical consequences of CYP2D6 polymorphisms.