著者

Takaaki Ishikawa Takahiro Shinozaki Kazutaka Shimoda

出版者

日本臨床精神神経薬理学会

雑誌

Clinical Neuropsychopharmacology and Therapeutics (ISSN:18848826)

巻号頁・発行日

vol.5, pp.18-22, 2014-07-15 (Released:2014-07-15)

参考文献数

11

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The patient was a 67-year-old man. After the patient received a diagnosis of schizophrenia, various antipsychotics were prescribed but did not improve symptoms. However, 18 mg/day aripiprazole (APZ) was found to be highly effective and enabled the patient to continue treatment on an outpatient basis. Two weeks after prescribing clarithromycin for fever and cough, he was readmitted to our psychiatric ward because of anuresis and deterioration of bradykinesia and salivation. Biochemical analysis revealed elevated serum creatine phosphokinase (26060 U/I) and creatinine (2.2 mg/dL). On admission, the patient had a high blood concentration of APZ and its metabolite(s). APZ was therefore discontinued, but the concentration remained elevated until day 8. Hemodialysis was started on day 4 to treat persistent renal dysfunction. The patient's CYP2D6 genotype was CYP2D6*10/CYP2D6*10. The elevated APZ levels may have resulted from the inhibitory action of clarithromycin on CYP3A4 combined with the lower inherent CYP2D6 enzymatic activity of the CYP2D6*10/CYP2D6*10 genotype.

著者

Yumiko Akamine Kayoko China Tsukasa Uno

出版者

日本臨床精神神経薬理学会

雑誌

Clinical Neuropsychopharmacology and Therapeutics (ISSN:18848826)

巻号頁・発行日

vol.3, pp.8-14, 2012 (Released:2012-05-11)

参考文献数

53

被引用文献数

1

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At the Blood–Brain barrier (BBB), the superfamily of ATP-binding cassette (ABC) transporters includes the ABCB1 subfamily corresponding to P-glycoprotein (P-gp), the ABCC subfamilies of multidrug resistance-associated proteins (MRPs), and the ABCG2 subfamily corresponding to breast cancer resistance protein (BCRP). These efflux transporters are located mainly in the endothelial cells forming the BBB and prevent the entry of xenobiotics into the brain. Since psychotropics act on target sites of the central nervous system (CNS) in the brain, it is very important to know these transporters' roles at the BBB and to determine the brain drug concentrations at the targeted sites of the CNS. However, there is little information on human brain concentrations of psychotropics. Recent studies have demonstrated that brain concentrations of many psychotropics are significantly higher in P-gp-knockout mice than in wild-type mice. This result implies that P-gp may be a key player in the regulation of brain psychotropic pharmacokinetics and possibly causes the P-gp-mediated drug interaction at the BBB. In this review, we discuss the current findings concerning the role of drug transporters on the concentrations of psychotropics in the brain and summarize the available in vivo studies related to psychotropics.

著者

Takashi Watanabe Yuki Hayashi Akiko Aoki Shin Ishiguro Mikito Ueda Kazufumi Akiyama Kazuko Kato Yoshimasa Inoue Shoko Tsuchimine Norio Yasui-Furukori Kazutaka Shimoda

出版者

日本臨床精神神経薬理学会

雑誌

Clinical Neuropsychopharmacology and Therapeutics (ISSN:18848826)

巻号頁・発行日

vol.6, pp.5-15, 2015 (Released:2015-03-13)

参考文献数

39

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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.