Simultaneous Determination of Methadone, Fluoxetine, Venlafaxine and Their Metabolites in Rat Plasma by UPLC–MS/MS for Drug Interaction Study

Pan, Peipei; Wang, Shuanghu; Wang, Jun; Luo, Jun; Geng, Peiwu; Zhou, Yunfang; Hu, Guoxin

doi:10.1007/s10337-016-3062-8

Cited by 12 publications

(5 citation statements)

References 24 publications

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“…After the administration of a single oral dose, more than half of the dose was metabolized to ODV, mainly through CYP2D6. 12 Both VEN and ODV are bioactive in vivo. When CYP2D6 is inhibited by other drugs, such as vonoprazan, the biotransformation of VEN might be affected, thereby, increasing the chance of the treatment being compromised by adverse reactions.…”

Section: Introductionmentioning

confidence: 99%

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

Chen¹,

Jiang²,

Xu³

et al. 2020

DDDT

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Purpose The purpose of the present study was to investigate the effects of vonoprazan on the pharmacokinetics of venlafaxine in vitro and in vivo. Methods The mechanism underlying the inhibitory effect of vonoprazan on venlafaxine was investigated using rat liver microsomes. In vitro, the inhibition was evaluated by determining the production of O-desmethylvenlafaxine. Eighteen male Sprague–Dawley rats were randomly divided into three groups: control group, vonoprazan (5 mg/kg) group, and vonoprazan (20 mg/kg) group. A single dose of 20 mg/kg venlafaxine was administrated to rats orally without or with vonoprazan. Plasma was prepared from blood samples collected via the tail vein at different time points and concentrations of venlafaxine and its metabolite, O-desmethylvenlafaxine, were determined by ultra-performance liquid chromatography-tandem mass spectrometry. Results We observed that vonoprazan could significantly decrease the amount of O-desmethylvenlafaxine (IC 50 = 5.544 μM). Vonoprazan inhibited the metabolism of venlafaxine by a mixed inhibition, combining competitive and non-competitive inhibitory mechanisms. Compared with that in the control group (without vonoprazan), the pharmacokinetic parameters of venlafaxine and its metabolite, O-desmethylvenlafaxine, were significantly increased in both 5 and 20 mg/kg vonoprazan groups, with an increase in MR O-desmethylvenlafaxine . Conclusion Vonoprazan significantly alters the pharmacokinetics of venlafaxine in vitro and in vivo. Further investigations should be conducted to check these effects in humans. Therapeutic drug monitoring of venlafaxine in individuals undergoing venlafaxine maintenance therapy is recommended when vonoprazan is used concomitantly.

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Section: Introductionmentioning

confidence: 99%

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

Chen¹,

Jiang²,

Xu³

et al. 2020

DDDT

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“…Plasma methadone levels were determined by ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) according to the validated method we published before with methadone and EDDP determined. The analytes were separated on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) and the mobile phase was acetonitrile and 0.1% formic acid in water in gradient elution at a flow rate of 0.40 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Silibinin affects the pharmacokinetics of methadone in rats

Pan

Wang²,

Luo

et al. 2017

Drug Testing and Analysis

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The aim of the present study was to investigate the pharmacokinetic effect of silibinin on methadone in rats. Twenty-four male Sprague-Dawley rats were randomly divided into 4 groups: control group, single dose of 100 mg/kg group, multiple doses of 100 mg/kg group, and multiple doses of 30 mg/kg group. A single dose of 6 mg/kg methadone was administrated to rats orally without or with silibinin. Plasma samples were collected via tail vein at different time points and concentrations of methadone and its metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), were determined by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Compared with the control group (without silibinin), both 30 and 100 mg/kg silibinin significantly increased the C of methadone, but only 100 mg/kg silibinin significantly increased the AUC of methadone and decreased its clearance. Pharmacokinetics parameters of EDDP were not altered by 30 mg/kg silibinin; its T was decreased by 100 mg/kg silibinin and the C was increased by single dose of 100 mg/kg silibinin. It is concluded that silibinin significantly altered the pharmacokinetics of methadone in rats by increasing the exposure of methadone. Further investigations in human should be conducted. Therapeutic drug monitoring of methadone in individuals undergoing methadone maintenance therapy is recommended when silibinin is concomitant.

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“…The validation of a UPLC-MS/ESI method developed for simultaneous determination of VEN and ODV in rat plasma and its use in pK studies in male Wistar rats, after administering the VEN solution orally, has been carried out by Dubey et al (2013) 34 . Pan et al (2016) claimed to have developed a fully validated UPLC-MS/MS method for simultaneous estimation of methadone, uoxetine, VEN and their metabolites in spiked rat plasma for drug interaction study and additionally applied it to pK studies as well 35 . 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 .…”

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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Simultaneous Determination of Methadone, Fluoxetine, Venlafaxine and Their Metabolites in Rat Plasma by UPLC–MS/MS for Drug Interaction Study

Cited by 12 publications

References 24 publications

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

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

Silibinin affects the pharmacokinetics of methadone in rats

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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