Saeki Yoshinori, Watanabe Takashi, Ueda Mikito, Saito Atsushi, Akiyama Kazufumi, Inoue Yoshimasa, Hirokane Genta, Morita Sachiyo, Yamada Naoto, Shimoda Kazutaka
Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, 321-0293, Japan.
Eur J Clin Pharmacol. 2009 Jul;65(7):685-91. doi: 10.1007/s00228-009-0633-8. Epub 2009 Mar 4.
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).
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).
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 x [plasma concentration of PAX (ng/ml)] - 33.0 x (L/S = 1, S/S = 0) - 21.8 x (with comorbid physical illness = 1, without comorbid physical illness = 0).
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.
本研究的目的是评估影响日本惊恐障碍（PD）患者帕罗西汀（PAX）初始药物治疗效果的遗传和药代动力学因素。
采用高效液相色谱法测定PAX的血浆浓度。通过聚合酶链反应技术测定5-羟色胺转运体基因连锁多态性区域（5-HTTLPR）变异。使用惊恐和场所恐惧症量表（PAS）评估PD严重程度。
多元回归分析显示，PAX的血浆浓度、5-HTTLPR基因型和共病躯体疾病是影响PAX对PD初始药物治疗效果的重要因素，表明这些因素占PAS评分降低百分比变异性的52.4%（R² = 0.524）。最终模型由以下方程描述（P = 0.001）：PAS评分降低百分比（%）= 68.5 - 1.2 × [PAX血浆浓度（ng/ml）] - 33.0 ×（L/S = 1，S/S = 0） - 21.8 ×（有共病躯体疾病 = 1，无共病躯体疾病 = 0）。
PAX的高血浆浓度、5-HTTLPR的L/S基因型和共病躯体疾病可能与PAX对PD药物治疗初始阶段反应不佳有关。
