A validated simultaneous quantification method for vonoprazan (TAK-438F) and its 4 metabolites in human plasma by the liquid chromatography-tandem mass spectrometry

Yoneyama, T; Teshima, Koichiro; Jinno, Fumihiro; Kondo, Takahiro; Asahi, Satoru

doi:10.1016/j.jchromb.2016.01.051

Cited by 22 publications

(15 citation statements)

References 10 publications

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“…Several studies have demonstrated that the primary metabolite of vonoprazan is mainly M-I and that M-I is further metabolized into M-II. M-I and M-II conjugate with glucuronic acid to form M-I-G and M-II-G [ 1 , 9 , 11 ]. Thus, M-I formation was measured to characterize the metabolism of vonoprazan in the hepatic microsomes of rats, dogs, and humans.…”

Section: Methodsmentioning

confidence: 99%

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Physiologically based pharmacokinetic–pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous/oral administration to rats, dogs and humans

et al. 2020

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Vonoprazan is characterized as having a long-lasting antisecretory effect on gastric acid. In this study we developed a physiologically based pharmacokinetic (PBPK)-pharmacodynamic (PD) model linking to stomach to simultaneously predict vonoprazan pharmacokinetics and its antisecretory effects following administration to rats, dogs, and humans based on in vitro parameters. The vonoprazan disposition in the stomach was illustrated using a limited-membrane model. In vitro metabolic and transport parameters were derived from hepatic microsomes and Caco-2 cells, respectively. We found the most predicted plasma concentrations and pharmacokinetic parameters of vonoprazan in rats, dogs and humans were within twofold errors of the observed data. Free vonoprazan concentrations ( f u × C 2 ) in the stomach were simulated and linked to the antisecretory effects of the drug ( I ) (increases in pH or acid output) using the fomula dI / dt = k × f u × C 2 × ( I max − I ) − k d × I . The vonoprazan dissociation rate constant k d (0.00246 min −1 ) and inhibition index K I (35 nM) for H + /K + -ATPase were obtained from literatures. The vonoprazan-H + /K + -ATPase binding rate constant k was 0.07028 min −1 · μM −1 using ratio of k d to K I . The predicted antisecretory effects were consistent with the observations following intravenous administration to rats (0.7 and 1.0 mg/kg), oral administration to dogs (0.3 and 1.0 mg/kg) and oral single dose or multidose to humans (20, 30, and 40 mg). Simulations showed that vonoprazan concentrations in stomach were 1000-fold higher than those in the plasma at 24 h following administration to human. Vonoprazan pharmacokinetics and its antisecretory effects may be predicted from in vitro data using the PBPK-PD model of the stomach. These findings may highlight 24-h antisecretory effects of vonoprazan in humans following single-dose or the sustained inhibition throughout each 24-h dosing interval during multidose administration.

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Section: Methodsmentioning

confidence: 99%

“…M-I is also the primary metabolite of vonoprazan in humans, mainly catalyzed by cytochrome P450 3A4 [ 9 ]. Several reports have demonstrated that the plasma exposure of M-I is the highest among the indicated metabolites [ 9 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Physiologically based pharmacokinetic–pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous/oral administration to rats, dogs and humans

et al. 2020

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“…The high‐performance liquid chromatography column was an Acquity UPLC BEH C18 (2.1 mm I.D., 100 mm, particle size 1.7 μm; Waters Corp.) maintained at 40 ◦ C. The isocratic mobile phase consisted of acetonitrile/20 mmol/L ammonium formate (pH 3) (32:68, v/v). The flow rate of the mobile phase was 0.4 mL/min, and the total run time was 5.0 minutes 26 . The calibration curve included 9 concentrations within the validation range, and the accuracy and precision of the method was assessed with quality control samples at concentrations of 0.1, 0.25, 5, and 80 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Food on the Pharmacokinetics of the Potassium‐Competitive Acid Blocker Vonoprazan

Mulford¹,

Leifke²,

Hibberd³

et al. 2021

Clinical Pharm in Drug Dev

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Herein,we report a food-effect study of vonoprazan,an oral potassium-competitive acid blocker.In a phase 1,randomized, open-label, crossover study, healthy subjects received a single 20-mg dose of vonoprazan either following an overnight fast or 30 minutes after a high-fat breakfast. Plasma vonoprazan levels were determined at 0 hour and at 17 subsequent assessment points up to 48 hours after dosing. After a 5-day washout, subjects received a second 20-mg vonoprazan dose in the alternative fed/fasted state (identical process repeated). Twenty-four subjects completed the study. Vonoprazan exposure was not meaningfully affected by food. Geometric mean ratios for maximum concentration, area under the concentration-time curve from time 0 to 24 hours, and area under the plasma concentration-time curve extrapolated to infinity obtained under fed and fasting conditions were 1.05 (90% confidence interval, 0.98-1.12), 1.13 (1.09-1.18), and 1.15 (1.11-1.19), respectively. Four subjects experienced 6 adverse events that were all mild and considered unrelated to the study drug. Vonoprazan can be administered without regard to food intake.

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“… 5 It is reported that vonoprazan has a promising prospect for clinical application as it can be absorbed faster and has a longer half-life with stronger and longer-lasting antigastric acid secretion effect, compared to the traditional PPIs. 6 …”

Section: Introductionmentioning

confidence: 99%

Effects of Simvastatin on the Metabolism of Vonoprazan in Rats Both in vitro and in vivo

Hong¹,

Dai²,

Cai³

et al. 2022

DDDT

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A validated simultaneous quantification method for vonoprazan (TAK-438F) and its 4 metabolites in human plasma by the liquid chromatography-tandem mass spectrometry

Cited by 22 publications

References 10 publications

Physiologically based pharmacokinetic–pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous/oral administration to rats, dogs and humans

Physiologically based pharmacokinetic–pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous/oral administration to rats, dogs and humans

The Effect of Food on the Pharmacokinetics of the Potassium‐Competitive Acid Blocker Vonoprazan

Effects of Simvastatin on the Metabolism of Vonoprazan in Rats Both in vitro and in vivo

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