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 language||English (US)|
|Number of pages||7|
|Journal||European journal of clinical pharmacology|
|State||Published - Jul 2009|
- Panic disorder
ASJC Scopus subject areas
- Pharmacology (medical)