&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 8 publications

(4 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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“…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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“…An effective UHPLC-MS/MS method for the simultaneous quanti cation of VEN and its ve metabolites in rat plasma have been reported by Gu et al (2018) and simultaneously applied it for pK study of VEN orally administered to rats 36 . Chen et al (2020) has reported a UPLC-MS/MS method to investigate the underlying mechanism of effect of vonoprazan on VEN in rat liver microsomes along with its impact on pK pro le of VEN and ODV in male Sprague-Dawley rats after oral administration of drugs 37 . An SPE based gas chromatography mass spectrometric (GC-MS) method for the estimation of venlafaxine in rat plasma and its application to assess pK interaction between VEN and uoxetine in Sprague-Dawley rats has been reported by Song et al (2017) 38 .…”

Section: Venlafaxine (Ven) (Rs) 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol Which Belongs Tomentioning

confidence: 99%

Tandem Mass Spectrometry (MS/MS) in the Preclinical Pharmacokinetic Study of a Highly Prescribed SNRI Drug for Depression and Its Application to Oral Extended Release Solid Dosage Formulations in Rabbits

Fazli

Panigrahy

Kumar

et al. 2021

Preprint

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Preclinical pharmacokinetic (pK) studies in animal models during the formulation development phase give preliminary evidence and near clear picture of the pK behavior of drug and/or its dosage forms prior to clinical studies on humans and help in tailoring of the dosage form according to the expected and requisite clinical behavior. The present work reports first of its kind preclinical pK study on oral extended release (ER) solid dosage formulations of venlafaxine (VEN) in New Zealand White rabbits. The VEN is a highly prescribed and one of the safest and most effective therapeutic agents used in the treatment different types of depression disorders worldwide. The LC-MS/MS bioanalytical method developed for this purpose demonstrated enough reliability in simultaneously quantitating VEN and its equipotent metabolite O-desmethylvenlafaxine (ODV) in rabbit plasma. The method described uses solid phase extraction for sample preparation followed by an ultra-fast LC-MS/MS analysis. The chromatographic separation was achieved isocratically with a predominantly polar mobile phase by employing RPLC. The triple quadrupole LC/MS/MS system operated in MRM mode used an ESI probe as an ion source in positive polarity. The validation results are within the permissible limits of US FDA recommendations and acceptance criteria for bioanalytical method validation.

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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 8 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

Application of Intranasal Administration in the Delivery of Antidepressant Active Ingredients

Tandem Mass Spectrometry (MS/MS) in the Preclinical Pharmacokinetic Study of a Highly Prescribed SNRI Drug for Depression and Its Application to Oral Extended Release Solid Dosage Formulations in Rabbits

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