Therapeutic Reference Range for Plasma Concentrations of Paroxetine in Patients With Major Depressive Disorders

Tomita, Tetsu; Yasui‐Furukori, Norio; Nakagami, Taku; Tsuchimine, Shoko; Ishioka, Masamichi; Kaneda, Ayako; Nakamura, Kazuhiko; Kaneko, Sunao

doi:10.1097/ftd.0000000000000036

Cited by 19 publications

(19 citation statements)

References 44 publications

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“…35) In the present study, the IC 50 value (0.35-0.45 µM) of paroxetine for blocking I HERG is higher than the therapeutic plasma concentrations. However, significant inhibition of I HERG at concentrations of 0.1 µM paroxetine was detected.…”

Section: ) Discussionmentioning

confidence: 91%

Blockade of HERG Human K<sup>+</sup> Channels by the Antidepressant Drug Paroxetine

Lee

Sung

Lee

et al. 2014

Biological & Pharmaceutical Bulletin

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The effects of paroxetine, a selective serotonin reuptake inhibitor, on human ether-a-go-go-related gene (HERG) channels were investigated using the whole-cell patch-clamp technique. The HERG channels were stably expressed in human embryonic kidney cells. Paroxetine inhibited the peak tail currents of the HERG channel in a concentration-dependent manner, with an IC 50 value of 0.45 µM and a Hill coefficient of 0.85. These effects were reversible after wash-out of the drug. The paroxetine-induced inhibition of the HERG channels was voltage-dependent. There was a steep increase in inhibition over the voltage range of the channel opening. Also, a shallow voltage-dependent inhibition was detected over the voltage range in which the channels were fully activated. The fractional electrical distance was estimated to be 0.11. Paroxetine induced a leftward shift in the voltage-dependence of the steady-state activation of the HERG channels. Before and after application of the 1 µM paroxetine, the half-maximum activation was 14.21 mV and 27.04 mV, respectively, with no shift in the slope value. The HERG channel block was not use-dependent. The characteristics of the block were dependent on open and inactivated channel states rather than closed state. Paroxetine had no effect on activation and deactivation kinetics, steady-state inactivation. These results suggest that paroxetine blocks the HERG channels by binding to these channels in the open and inactivated states.

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Section: ) Discussionmentioning

confidence: 91%

Blockade of HERG Human K<sup>+</sup> Channels by the Antidepressant Drug Paroxetine

Lee

Sung

Lee

et al. 2014

Biological & Pharmaceutical Bulletin

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“…BrainSpheres were exposed to therapeutic-relevant paroxetine concentrations (Tomita et al, 2014) for the 8 weeks of differentiation. After 8 weeks of treatment, BrainSpheres were collected, fixed and stained with different antibodies as described in materials and methods.…”

Section: Paroxetine Exposure Alters the Expression Of Synaptic Markermentioning

confidence: 99%

“…In this study, we used the BrainSphere model to study the effects of paroxetine on different processes of brain development. Exposure to humanrelevant therapeutic blood concentrations of paroxetine (Tomita et al, 2014) led to alterations in synaptic markers expression, myelination, neurite outgrowth and oligodendrocyte numbers in BrainSpheres differentiated from two independent iPSCs lines, strongly suggesting paroxetine as a DNT toxicant.…”

Section: Introductionmentioning

confidence: 99%

Antidepressant Paroxetine Exerts Developmental Neurotoxicity in an iPSC-Derived 3D Human Brain Model

Zhong

Harris

Smirnova

et al. 2020

Front. Cell. Neurosci.

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“…Whereas, we dealt all data with patients treated with paroxetine monotherapy regardless in its response and we investigated the continuous variables for each parameter. The result that no association between plasma On the other hand, Tomita et al reported the responder and remitter rates of the patients according to their plasma paroxetine concentrations: 20 ng/mL, 40 ng/mL and 60 ng/ml, and found the 20-60 ng/mL plasma paroxetine group showed highest response [7]. Yasui-Furukori reported that plasma paroxetine concentrations are negatively associated with improvement and that response occurs at the upper threshold of 64.2 ng/ml of paroxetine [8].…”

Section: Discussionmentioning

confidence: 96%

Serum Brain-Derived Neurotrophic Factor Level, Plasma 3-Methoxy-4-Hydroxyphenylglycol Level in Major Depressed Patients with Paroxetine Monotherapy

Yoshimura

Atake²,

Hori³

et al. 2016

J Depress Anxiety

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Statistical AnalysisRelations between the clinical response, serum biomarkers, and paroxerine levels were analyzed using Spearman correlation. In addition, findings were corrected for multiple comparisons via Bonferroni correction. Significance of results was set at p<0.05. Result Changes of the HAMD17 scores and plasma MHPG levelsNo association was found between the HAMD17 scores and plasma MHPG levels (rho=-0.0774, p=0.8413) (Figure 1). AbstractObjective: We investigated the relationships among clinical efficacy, brain-derived neurotrophic factor (BDNF), 3-methoxy-4-hydroxyphenylglycol (MHPG), and paroxetine concentration in patients with major depressive disorder (MDD) who treated with paroxetine monotherapy.

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Therapeutic Reference Range for Plasma Concentrations of Paroxetine in Patients With Major Depressive Disorders

Abstract: The results of this study suggested that a range of 20-60 ng/mL is the therapeutic reference range for concentrations of paroxetine in plasma in patients with MDD.

Cited by 19 publications

References 44 publications

Blockade of HERG Human K<sup>+</sup> Channels by the Antidepressant Drug Paroxetine

Blockade of HERG Human K<sup>+</sup> Channels by the Antidepressant Drug Paroxetine

Antidepressant Paroxetine Exerts Developmental Neurotoxicity in an iPSC-Derived 3D Human Brain Model

Serum Brain-Derived Neurotrophic Factor Level, Plasma 3-Methoxy-4-Hydroxyphenylglycol Level in Major Depressed Patients with Paroxetine Monotherapy

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