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 language | English (US) |
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Pages (from-to) | 685-691 |
Number of pages | 7 |
Journal | European journal of clinical pharmacology |
Volume | 65 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2009 |
Externally published | Yes |
Keywords
- 5-HTTLPR
- Panic disorder
- Paroxetine
- Pharmacotherapy
- SSRIs
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)