[Show abstract][Hide abstract] ABSTRACT: Purpose: This study evaluated the impact of CYP2D6 polymorphism, and particularly CYP2D6*10 alleles, on the steady-state plasma concentrations of mirtazapine (MIR) and its metabolite N-desmethylmirtazapine (DMIR) in Japanese psychiatric patients.Patients and Methods: The subjects were 75 Japanese patients treated with racemic MIR. The steady-state plasma concentrations of MIR and DMIR were measured using liquid chromatography. The CYP2D6 genotypes were determined by polymerase chain reaction. Three subjects whose plasma levels of MIR and DMIR were below the limit of detection were regarded as non-adherent and excluded, and 4 subjects having the CYP2D6*5 allele (CYP2D6*1/CYP2D6*5 and CYP2D6*2/CYP2D6*5 (n = 3) and CYP2D6*5/CYP2D6*10 (n = 1)) were excluded from the analysis in order to eliminate the effect of the CYP2D6*5 allele. Accordingly, data from 68 subjects were subjected to analysis.Results: There were no significant differences in the plasma concentrations of MIR or DMIR (all corrected for dose and body weight) among different CYP2D6 genotypes. Multiple regression analysis also revealed that age affects MIR (corrected for dose and body weight) (p=0.079). Also, multiple regression analysis revealed that age correlated significantly to the plasma concentration of DMIR (corrected for dose and body weight) (p=0.026). Neither sex nor the number of CYP2D6*10 alleles were significant factors for either the plasma concentration of MIR (corrected for dose and body weight) or the plasma concentration of DMIR (corrected for dose and body weight).Conclusion: CYP2D6*10 polymorphism did not significantly affect the steady-state plasma levels of MIR and DMIR in Japanese patients, but age had a significant effect on the plasma levels of DMIR.
[Show abstract][Hide abstract] ABSTRACT: Objective
The aims of the present study were to analyze the association between discontinuation of paroxetine (PAX) and the genetic variants of the polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in Japanese patients with panic disorder (PD) and major depressive disorder (MDD).
The 5-HTTLPR genotype was determined by polymerase chain reaction method. PAX plasma concentration was measured by high-performance liquid chromatography to confirm adherence.
When comparing between the PD and MDD patients with the chi-square test and Fisher’s exact test, the PD patients had a significant and higher discontinuation rate due to non-adherence than did the MDD patients (13.5% [7/52] versus 0% [0/88], respectively; P<0.001). MDD patients had a significant and higher discontinuation rate due to untraceability than PD patients (12.5% [11/88] versus 1.9% [1/52]; P=0.032). Multilogistic regression revealed a tendency for the long/short and short/short genotypes to affect discontinuation due to adverse effects in PD patients (25.0% versus 6.3%, respectively; P=0.054).
The results indicate that the 5-HTTLPR genotype might contribute to the discontinuation of initial PAX treatment due to adverse effects in PD patients.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to evaluate genetic and pharmacokinetic factors to establish the pharmacotherapeutic effect of paroxetine (PAX) in patients with panic disorder (PD).
Subjects were 65 drug-naïve patients who fulfilled the DSM-IV-TR criteria for PD diagnosis. All subjects were administered PAX (10 mg/day) for 4 weeks, and PD severity was assessed using the Panic and Agoraphobia Scale (PAS) at baseline and at 2 and 4 weeks after initiation of treatment. Plasma PAX concentration was determined by high-performance liquid chromatography. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) variants and the -1019C/G promoter polymorphism of the serotonin 1A receptor (5-HT(1A)) gene were determined by PCR analysis.
Multiple regression analysis revealed that the plasma concentrations of PAX, 5-HTTLPR genotype, and -1019C/G 5-HT(1A) gene polymorphism were significant factors affecting clinical response to PAX (reduction ratio of PAS score) at 2 weeks after the initiation of pharmacotherapy. The -1019C/G 5-HT(1A) gene promoter polymorphism, PAS score at baseline, and adverse effects were found to be the significant factors affecting clinical response to PAX at 4 weeks after initiation of pharmacotherapy.
The present study revealed that plasma concentration of PAX, 5-HTTLPR genotype, -1019C/G 5-HT(1A) genotype, PAS score at baseline, and adverse effects may influence the therapeutic response to PAX in patients with PD.
European Journal of Clinical Pharmacology 06/2011; 67(12):1213-21. DOI:10.1007/s00228-011-1073-9 · 2.97 Impact Factor