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Genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine in Japanese patients with panic disorder

  • Pharmacogenetics
  • Published:
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Abstract

Objective

The objective of this study was to evaluate genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine (PAX) in Japanese patients with panic disorder (PD).

Method

Plasma concentration of PAX was determined by high performance liquid chromatography. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) variants were determined by polymerase chain reaction techniques. PD severity was assessed using the Panic and Agoraphobia Scale (PAS).

Results

Multiple regression analysis revealed that the plasma concentration of PAX, 5-HTTLPR genotype, and comorbid physical illness were significant factors affecting the initial pharmacotherapeutic effect of PAX in PD and indicated that these factors accounted for 52.4% (R 2 = 0.524) of the variability in the percent reduction in PAS score. The final model was described by the following equation (P = 0.001): percent reduction in PAS score (%) = 68.5 − 1.2 × [plasma concentration of PAX (ng/ml)] − 33.0 × (L/S = 1, S/S = 0) − 21.8 × (with comorbid physical illness = 1, without comorbid physical illness = 0).

Conclusion

The high plasma concentration of PAX, the L/S genotype of 5-HTTLPR, and comorbid physical illness might be associated with a poor response to the initial phase of pharmacotherapy of PD with PAX.

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Acknowledgements

This research was supported by KAKENHI, Grants-in-Aid for Scientific Research, and a Grant-in-Aid for Young Scientists from the Japan Society for the Promotion of Science (JSPS) (#18591307) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (#19790837 and #18790847). The authors are grateful to Ms. Yoshimi Aoyama for her excellent technical assistance. The authors have no conflicts of interest directly relevant to the content of the present study.

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Authors and Affiliations

  1. Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, 321–0293, Japan

    Yoshinori Saeki, Takashi Watanabe, Mikito Ueda & Kazutaka Shimoda

  2. Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321–0293, Japan

    Atsushi Saito & Kazufumi Akiyama

  3. MP Technopharma, 955 Koiwai, Yoshitomicho, Chikujo, Fukuoka, 871–8550, Japan

    Yoshimasa Inoue

  4. Department of Psychiatry, Shiga University of Medical Science, Seta Tsukinowacho, Otsu, Shiga, 520–2192, Japan

    Genta Hirokane, Sachiyo Morita & Naoto Yamada

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  1. Yoshinori Saeki
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  2. Takashi Watanabe
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Correspondence to Kazutaka Shimoda.

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Saeki, Y., Watanabe, T., Ueda, M. et al. Genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine in Japanese patients with panic disorder. Eur J Clin Pharmacol 65, 685–691 (2009). https://doi.org/10.1007/s00228-009-0633-8

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  • DOI: https://doi.org/10.1007/s00228-009-0633-8

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