&lt;p&gt;In Vitro and In Vivo Rat Model Assessments of the Effects of Vonoprazan on the Pharmacokinetics of Venlafaxine&lt;/p&gt;

Chen, Feifei; Jiang, Hui; Xu, Jia; Wang, Shuanghu; Meng, Deru; Geng, Peiwu; Dai, Da‐Peng; Zhou, Quan; Zhou, Yunfang

doi:10.2147/dddt.s276704

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…The results of in vitro studies indicated that vonoprazan could inhibit the metabolism of midazolam, the substrate of CYP3A4, and venlafaxine, the substrate of CYP3A4 and CYP2D6. In addition, the in vivo studies supported the results of the in vitro studies, which implicated the drug-drug interactions between vonoprazan and the substrates of CYP3A4 ( Chen et al, 2020 ; Wang et al, 2020 ). The half-maximal inhibitory concentration (IC50) value of CYP3A4 for vonoprazan was 29 μM, and this value is thought to be much higher than the plasma concentration of vonoprazan at clinical doses ( Nishihara et al, 2019 ).…”

Section: Introductionsupporting

confidence: 61%

Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects

Hwang

Lee

et al. 2021

Front. Pharmacol.

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Potassium-competitive acid blocker is a new class of drugs inhibiting gastric acid. It is controversial that vonoprazan showed the inhibitory activities of cytochrome P450 3A4. This study aimed to evaluate the pharmacokinetics (PK) of atorvastatin and safety when atorvastatin was administered alone and co-administered with vonoprazan or tegoprazan. An open-label, multiple-dose, 3-intervention, 4-sequence, 4-period, partial replicate crossover study was conducted, and three interventions were; one is orally administered atorvastatin 40 mg alone once daily for 7 days, another is atorvastatin co-administered with vonoprazan 20 mg, and the other is atorvastatin co-administered with tegoprazan 50 mg. PK blood samples were collected up to 24 h after the last dose, and PK parameters for atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were estimated by a non-compartmental method. Safety was evaluated, including adverse events and clinical laboratory tests. A total of 28 subjects completed the study. When atorvastatin was co-administered with vonoprazan, the systemic exposures of atorvastatin and atorvastatin lactone significantly increased, and the metabolic ratio of 2-hydroxyatorvastatin significantly decreased. Hypergastrinemia only occurred when atorvastatin was co-administered with vonoprazan. However, the plasma concentration profiles of atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were similar when atorvastatin was administered alone or co-administered with tegoprazan. In conclusion, after multiple doses of atorvastatin co-administered with vonoprazan in healthy subjects, the systemic exposure of atorvastatin and the incidence of hypergastrinemia increased. With tegoprazan, however, those interactions were not observed.

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Section: Introductionsupporting

confidence: 61%

Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects

Hwang

Lee

et al. 2021

Front. Pharmacol.

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“…C804424, purity>98%) was purchased from Macklin (Shanghai, China). RLMs were prepared in our laboratory ( Chen et al, 2020 ; Zhou et al, 2020 ). HLMs were purchased from PrimeTox (Wuhan, China).…”

Section: Methodsmentioning

confidence: 99%

Effects of bergapten on the pharmacokinetics of macitentan in rats both in vitro and in vivo

Zhou

Hou

et al. 2023

Front. Pharmacol.

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Macitentan was approved by the United States Food and Drug Administration (FDA) in 2013 for the treatment of pulmonary arterial hypertension (PAH). Bergapten is a furanocoumarin that is abundant in Umbelliferae and Rutaceae plants and is widely used in many Chinese medicine prescriptions. Considering the possible combination of these two compounds, this study is aimed to investigate the effects of bergapten on the pharmacokinetics of macitentan both in vitro and in vivo. Rat liver microsomes (RLMs), human liver microsomes (HLMs), and recombinant human CYP3A4 (rCYP3A4) were used to investigate the inhibitory effects and mechanisms of bergapten on macitentan in vitro. In addition, pharmacokinetic parameters were also studied in vivo. Rats were randomly divided into two groups (six rats per group), with or without bergapten (10 mg/kg), and pretreated for 7 days. An oral dose of 20 mg/kg macitentan was administered to each group 30 min after bergapten or 0.5% CMC-Na administration on day 7. Blood was collected from the tail veins, and the plasma concentrations of macitentan and its metabolites were assessed by ultra-performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). Finally, we analyzed the binding force of the enzyme and two small ligands by in silico molecular docking to verify the inhibitory effects of bergapten on macitentan. The in vitro results revealed that the IC50 values for RLMs, HLMs, and rCYP3A4 were 3.84, 17.82 and 12.81 μM, respectively. In vivo pharmacokinetic experiments showed that the AUC(0-t), AUC(0-∞), and Cmax of macitentan in the experimental group (20,263.67 μg/L*h, 20,378.31 μg/L*h and 2,999.69 μg/L, respectively) increased significantly compared with the control group (7,873.97 μg/L*h, 7,897.83 μg/L*h and 1,339.44 μg/L, respectively), while the CLz/F (1.07 L/h/kg) of macitentan and the metabolite-parent ratio (MR) displayed a significant decrease. Bergapten competitively inhibited macitentan metabolism in vitro and altered its pharmacokinetic characteristics in vivo. Further molecular docking analysis was also consistent with the experimental results. This study provides a reference for the combined use of bergapten and macitentan in clinical practice.

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“…Venlafaxine (VLF) inhibits central 5-HT and NE neuronal reuptake, thereby increasing levels in the synaptic cleft between neurons in the brain. Oral VLF has low bioavailability, a short half-life, delayed onset of action, and significant systemic adverse reactions [ 105 , 106 ]. Cayero-Otero et al prepared VLF-loaded PLGA-NPs and modified the nanoparticles with transferrin and specific peptide against transferrin receptor.…”

Section: Intranasal Administration Of Antidepressant Active Ingredientsmentioning

confidence: 99%

Application of Intranasal Administration in the Delivery of Antidepressant Active Ingredients

et al. 2022

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As a mental disease in modern society, depression shows an increasing occurrence, with low cure rate and high recurrence rate. It has become the most disabling disease in the world. At present, the treatment of depression is mainly based on drug therapy combined with psychological therapy, physical therapy, and other adjuvant therapy methods. Antidepressants are primarily administered peripherally (oral and intravenous) and have a slow onset of action. Antidepressant active ingredients, such as neuropeptides, natural active ingredients, and some chemical agents, are limited by factors such as the blood–brain barrier (BBB), first-pass metabolism, and extensive adverse effects caused by systemic administration. The potential anatomical link between the non-invasive nose–brain pathway and the lesion site of depression may provide a more attractive option for the delivery of antidepressant active ingredients. The purpose of this article is to describe the specific link between intranasal administration and depression, the challenges of intranasal administration, as well as studies of intranasal administration of antidepressant active ingredients.

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<p>In Vitro and In Vivo Rat Model Assessments of the Effects of Vonoprazan on the Pharmacokinetics of Venlafaxine</p>

Cited by 9 publications

References 27 publications

Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects

Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects

Effects of bergapten on the pharmacokinetics of macitentan in rats both in vitro and in vivo

Application of Intranasal Administration in the Delivery of Antidepressant Active Ingredients

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