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

Yoshinori Saeki, Takashi Watanabe, Mikito Ueda, Atsushi Saito, Kazufumi Akiyama, Yoshimasa Inoue, Genta Hirokane, Sachiyo Morita, Naoto Yamada, Kazutaka Shimoda

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)685-691
Number of pages7
JournalEuropean Journal of Clinical Pharmacology
Volume65
Issue number7
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

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Paroxetine
Panic Disorder
Pharmacokinetics
Agoraphobia
Panic
Genotype
Serotonin Plasma Membrane Transport Proteins
High Pressure Liquid Chromatography
Regression Analysis
Drug Therapy
Polymerase Chain Reaction
Genes

Keywords

  • 5-HTTLPR
  • Panic disorder
  • Paroxetine
  • Pharmacotherapy
  • SSRIs

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine in Japanese patients with panic disorder. / Saeki, Yoshinori; Watanabe, Takashi; Ueda, Mikito; Saito, Atsushi; Akiyama, Kazufumi; Inoue, Yoshimasa; Hirokane, Genta; Morita, Sachiyo; Yamada, Naoto; Shimoda, Kazutaka.

In: European Journal of Clinical Pharmacology, Vol. 65, No. 7, 01.07.2009, p. 685-691.

Research output: Contribution to journalArticle

Saeki, Yoshinori ; Watanabe, Takashi ; Ueda, Mikito ; Saito, Atsushi ; Akiyama, Kazufumi ; Inoue, Yoshimasa ; Hirokane, Genta ; Morita, Sachiyo ; Yamada, Naoto ; Shimoda, Kazutaka. / Genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine in Japanese patients with panic disorder. In: European Journal of Clinical Pharmacology. 2009 ; Vol. 65, No. 7. pp. 685-691.
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AU - Saeki, Yoshinori

AU - Watanabe, Takashi

AU - Ueda, Mikito

AU - Saito, Atsushi

AU - Akiyama, Kazufumi

AU - Inoue, Yoshimasa

AU - Hirokane, Genta

AU - Morita, Sachiyo

AU - Yamada, Naoto

AU - Shimoda, Kazutaka

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N2 - 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.

AB - 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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