ArticlePharmacogenomics and personalized medicine2014
Possible impact of the CYP2D6*10 polymorphism on the nonlinear pharmacokinetic parameter estimates of paroxetine in Japanese patients with major depressive disorders.
Article in Pharmacogenomics and personalized medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 12 citations in OpenAlex.
- Natural Polymorphic Variants in the CYP450 Superfamily: A Review of Potential Structural Mechanisms and Functional Consequences.International journal of molecular sciences · 2025Review
- Pharmacogenomics in Psychiatry Practice: The Value and the Challenges.International journal of molecular sciences · 2022Review
- Pharmacokinetics of immediate and sustained-release formulations of paroxetine: Population pharmacokinetic approach to guide paroxetine personalized therapy in chinese psychotic patients.Frontiers in pharmacology · 2022Article
- Genetic polymorphisms analysis of CYP2D6 in the Uygur population.BMC genomics · 2016Article
- Role of cytochrome P450 2D6 genetic polymorphism in carvedilol hydroxylation in vitro.Drug design, development and therapy · 2016Article
- Cytochrome P450 2D6 genotype affects the pharmacokinetics of controlled-release paroxetine in healthy Chinese subjects: comparison of traditional phenotype and activity score systems.European journal of clinical pharmacology · 2015Article
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6 authors at 2 institutions in 1 country.
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Abstract
It has been suggested that the reduced function allele with reduced cytochrome P450 (CYP) 2D6 activity, CYP2D6*10, is associated with the interindividual differences in the plasma paroxetine concentrations, but there is no data presently available regarding the influence of the CYP2D6*10 polymorphism on the pharmacokinetic parameters, eg, Michaelis-Menten constant (Km) and maximum velocity (Vmax), in Asian populations. The present study investigated the effects of the CYP2D6 polymorphisms, including CYP2D6*10, on the pharmacokinetic parameters of paroxetine in Japanese patients with major depressive disorders. This retrospective study included 15 Japanese patients with major depressive disorders (four males and eleven females) who were treated with paroxetine. The CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41 polymorphisms were evaluated. A total of 56 blood samples were collected from the patients. The Km and Vmax values of paroxetine were estimated for each patient. The allele frequencies of CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41 were 6.7%, 0%, 10.0%, 56.7%, 0%, 26.7%, and 0%, respectively. The mean values of Km and Vmax were 50.5±68.4 ng/mL and 50.6±18.8 mg/day, respectively. Both the Km and Vmax values were significantly smaller in CYP2D6*10 allele carriers than in the noncarriers (24.2±18.3 ng/mL versus 122.5±106.3 ng/mL, P=0.008; 44.2±16.1 mg/day versus 68.3±15.0 mg/day, P=0.022, respectively). This is the first study to demonstrate that the CYP2D6*10 polymorphism could affect the nonlinear pharmacokinetic parameter estimates of paroxetine in Asian populations. The findings of this study suggest that the CYP2D6*10 polymorphism may be associated with the smaller values of both the Km and Vmax in Japanese patients with major depressive disorders, and these results need to be confirmed in further investigations with a larger number of patients.
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