Pharmacokinetics and Safety of Vortioxetine in the Chinese Population

Miao, Jia; Wang, Gang; Hou, Jie; Areberg, Johan; Zhao, Yan; Højer, Astrid-Maria; Ettrup, Anders

doi:10.1007/s12325-019-01092-4

Cited by 8 publications

(7 citation statements)

References 24 publications

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“…Factors such as age, sex, race/ethnicity, body weight, and liver or kidney impairment had no clinically significant effects on vortioxetine exposure (23). For example, no clinically meaningful difference in the pharmacokinetics of vortioxetine was observed between the data obtained from a study conducted in the Chinese population and previous data of a non-Chinese population (24).…”

Section: Editorialmentioning

confidence: 83%

Vortioxetine: a comprehensive update on a new-generation antidepressant

Evren¹

2021

Dusunen Adam

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The combined mechanisms of action of new-generation antidepressants may provide greater therapeutic benefits (14).New-generation antidepressants were designed with the goal of optimizing treatment efficacy and tolerability. Vortioxetine is one of the new antidepressants with multimodal activity (10). It is the first mixed serotonin agonist and antagonist antidepressant (7). It has been approved for the treatment of MDD in many countries, including European nations (15) and the United States (16). The antidepressant mechanism of action of vortioxetine combines serotonin transporter (5-HTT) inhibition and direct modulation of serotonin receptor activity; it is a 5-HT1A receptor agonist; a 5-HT1B receptor partial agonist; a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist; and a 5-HTT inhibitor (14,17,18). These additional serotonin receptor targets distinguish vortioxetine from other SSRIs and SNRIs, and this activity may provide unique clinical benefits for symptomatic recovery in MDD patients ( 7). Vortioxetine increases the extracellular concentration of various neurotransmitters, such as dopamine, histamine, noradrenaline, and acetylcholine, in addition to providing a regulatory effect on serotonin receptors and 5-HTT (14,18). The serotonin system has a positive effect on mood, affect, and cognition. Vortioxetine also modulates key neurotransmitters involved in cognitive regulation, such as glutamate, acetylcholine, histamine, dopamine, and noradrenaline (17). Dose and PharmacokineticsVortioxetine is available in 5-, 10-, and 20-mg tablets. Vortioxetine was found to be less effective at low doses of 2.5-5 mg, while a dose range of 5-20 mg is effective (17). The maximum dose of 20 mg vortioxetine has demonstrated a better clinical response than lower doses (19)(20)(21)(22). However, the 20-mg dose has also been associated with a higher risk of side effects ( 14). An initial 10-mg dose once a day may be increased to 20 mg according to tolerability and clinical response (14). The pharmacokinetics of vortioxetine are linear and dose-proportional (23). Since the binding rate of vortioxetine to plasma proteins is 80-90%, it has a wide distribution volume (steady-state distribution volume of approximately 2600 L) (14,23). It has been reported that vortioxetine at higher doses (20 mg) was significantly superior to a placebo ( 14). It takes 3-16

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Section: Editorialmentioning

confidence: 83%

Vortioxetine: a comprehensive update on a new-generation antidepressant

Evren¹

2021

Dusunen Adam

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“…In a previous study, the maximal plasma concentration following multiple doses of 5, 10, or 20 mg was estimated to be 9 (0.024 μM), 18 (0.047 μM), and 33 ng/mL (0.087 μM) [ 57 ]. Other reports demonstrated that maximal plasma level following the VOR administration could reach 50 ng/mL (0.13 μM) [ 49 , 58 ]. Those values tend to be lower than the IC 50 or K D value for VOR-mediated inhibition of I K(DR) described herein.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effectiveness in Delayed-Rectifier Potassium Current Caused by Vortioxetine, Known to Be a Novel Antidepressant

Hsiao

Wang

2022

Biomedicines

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Vortioxetine (VOR) is recognized to exert antidepressant actions. However, whether this drug modifies ionic currents in excitable cells remains unclear. The aim of this study was to explore the electrophysiological effects of VOR and other related compounds in pituitary GH3 cells and in Neuro-2a cells. VOR suppressed the delayed-rectifier K+ current (IK(DR)) in a concentration-, time-, and state-dependent manner. Effective IC50 values needed to inhibit peak and sustained IK(DR) were computed to be 31.2 and 8.5 μM, respectively, while the KD value estimated from minimal binding scheme was 7.9 μM. Cell exposure to serotonin (10 μM) alone failed to alter IK(DR), while fluoxetine (10 μM), a compound structurally similar to VOR, mildly suppressed current amplitude. In continued presence of VOR, neither further addition of propranolol nor risperidone reversed VOR-mediated inhibition of IK(DR). Increasing VOR concentration not only depressed IK(DR) conductance but also shifted toward the hyperpolarized potential. As the VOR concentration was raised, the recovery of IK(DR) block became slowed. The IK(DR) activated by a downsloping ramp was suppressed by its presence. The inhibition of IK(DR) by a train pulse was enhanced during exposure to VOR. In Neuro-2a cells, this drug decreased IK(DR). Overall, inhibitory effects of VOR on ionic currents might constitute another underlying mechanism of its actions.

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“…The pharmacokinetic properties of VO have been studied in mice, rats, dogs, and in human subjects. 30 , 112 – 116 …”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The pharmacokinetic properties of VO have been studied in mice, rats, dogs, and in human subjects. 30,[112][113][114][115][116] In humans, the absolute bioavailability of VO, determined after intravenous and oral administrations to the same volunteers, was high (up to 75%) and independent of food intake. 117 VO shows a linear, dose-proportional and timeindependent pharmacokinetics at doses from 2.5 mg to 75 mg. 118 It has an extensive volume of distribution as the plasma protein binding is 80-90%.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Vortioxetine as a new frontier in the treatment of chronic neuropathic pain: a review and update

Adamo

Calabria

Coppola

et al. 2021

Therapeutic Advances in Psychopharmacology

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Chronic neuropathic pain (CNP) is a disabling medical condition that impairs the health-related quality-of-life of affected patients. A high prevalence of anxiety, depression, sleep disturbance and cognitive impairment has frequently been reported in association with CNP, making the management of this disease complex and often multidisciplinary. Dual-acting agents such as selective serotonin and noradrenalin reuptake inhibitors (SNRIs) are considered particularly useful in the modulation of pain and in treatment of the mood disorders frequently associated with CNP. Recent evidence suggests that the top-down inhibitory control of pain involves the engagement and enhancement of descending endogenous opioidergic, cannabinoid and serotonergic systems, with the effect of serotonin being particularly related to the receptor subtypes that are preferentially activated; indeed serotonin induces analgesia via activation of 5-HT7 receptors and hyperalgesia via activation of 5-HT3 receptors. Vortioxetine (VO) is a novel multimodal serotonergic antidepressant with a unique mechanism of action. It has been demonstrated recently in experimental and clinical studies to have efficacy on pain hypersensitivity and on mood disorders. This drug inhibits the serotonin transporter with a high affinity, antagonises the 5-HT3, 5-HT1D and 5HT7 serotonin receptors, and activates the 5-HT1A and 5-HT1B receptors. In clinical studies, VO has proved effective at a dose of 10–20 mg/daily in short- and long-term treatment of patients with chronic orofacial pain, demonstrating a higher rate of clinical response and remission, a better acceptability, safety rate and tolerability, and a lower latency of action compared with other antidepressants. In the light of these recent findings, VO may be considered as a new pharmacological treatment also in relation to various types of CNP, particularly in elderly patients with concomitant mood disorders and cognitive impairment. The purpose of this review is to provide an up-to-date overview of the pharmacology and clinical applications of VO and to highlight its potential therapeutic properties and advantages in the management of CNP.

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Pharmacokinetics and Safety of Vortioxetine in the Chinese Population

Cited by 8 publications

References 24 publications

Vortioxetine: a comprehensive update on a new-generation antidepressant

Vortioxetine: a comprehensive update on a new-generation antidepressant

Inhibitory Effectiveness in Delayed-Rectifier Potassium Current Caused by Vortioxetine, Known to Be a Novel Antidepressant

Vortioxetine as a new frontier in the treatment of chronic neuropathic pain: a review and update

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