Pharmacokinetics, pharmacodynamics, and safety of esomeprazole injection/infusion in healthy <scp>C</scp>hinese volunteers: A five‐way crossover study

Yang, Hong; Li, Jingnan; Zhao, Qian; Ji, Li; Shen, Kaikai; Yang, Xiaoou; Jiang, Ji; Hu, Pei; Qian, Jiaming

doi:10.1111/jgh.12305

Cited by 6 publications

(18 citation statements)

References 19 publications

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“…PPIs need time to reach their maximum efficacy because it takes time for the drug to accumulate in newly recruited parietal cells, and to maintain a steady state 22. In a human study, it was reported that the intragastric pH value fell below 4 after 15 hours and became unstable after a single IV injection of 40 mg esomeprazole, compared to twice‐daily administration and 24‐hour infusion groups 23. A recent study reported that esomeprazole inhibited gastric acid secretion in a dose‐dependent manner and the MPT that pH ≥4 was 59% after single administration of 1.6 mg/kg esomeprazole in dogs 8.…”

Section: Discussionmentioning

confidence: 98%

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Hwang

Jeong

Song

et al. 2017

Veterinary Internal Medicne

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BackgroundEsomeprazole is an S‐enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported.ObjectiveTo determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study).AnimalsSeven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively.MethodsBoth studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs.ResultsThe bioavailability of esomeprazole administered as PO enteric‐coated granules and as SC injections was 71.4 and 106%, respectively. The half‐life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05).ConclusionThe PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.

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Section: Discussionmentioning

confidence: 98%

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Hwang

Jeong

Song

et al. 2017

Veterinary Internal Medicne

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“…A washout period of 7 days separated the different dosing regimens. Subjects took standard food within 30 minutes at 4 hours and 9 hours postdose …”

Section: Methodsmentioning

confidence: 99%

“…The above measures ensured accurate measurement of plasma esomeprazole concentrations. Intragastric pH was recorded every 10 seconds from 0 to 24 hours postdose using a calibrated pH microelectrode placed approximately 10 cm below the lower esophageal sphincter . HP infection was diagnosed using the C urea breath test.…”

Section: Methodsmentioning

confidence: 99%

“…HP infection was diagnosed using the C urea breath test. The CYP2C19 genotype (homozygous extensive metabolizer [homozygote‐EM], heterozygous extensive metabolizer [heterozygote‐EM], or poor metabolizer [PM]) was determined by polymerase chain reaction−restriction fragment length polymorphism analysis …”

Section: Methodsmentioning

confidence: 99%

“…A clinical PK/PD study was conducted at our hospital to assess the efficacy and safety of esomeprazole after administration of five IV dosing regimens . CYP2C19 genotype and Helicobacter pylori (HP) status were also determined.…”

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confidence: 99%

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Pharmacokinetic and Pharmacodynamic Modeling Analysis of Intravenous Esomeprazole in Healthy Volunteers

Liu

Yang

Jiang

et al. 2016

The Journal of Clinical Pharmacology

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Esomeprazole is one of the most commonly used drugs to treat gastroesophageal reflux disease and peptic ulcers, but the quantitative relationships among the pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenomics (PG) of the drug are not fully understood in special patient populations. A clinical PK/PD/PG study of intravenous (IV) esomeprazole in 5 dosing regimens was conducted in 20 healthy Chinese volunteers, who were categorized into Helicobacter pylori (HP)-negative and HP-positive subgroups. Plasma esomeprazole concentration and intragastric H(+) concentration were monitored for 24 hours postdosing. Population PK (PopPK) models were tested based on elimination characteristics and other data. For a single-dose IV esomeprazole regimen, a 2-compartment model with nonlinear elimination characteristics fitted the PK data well. The elimination of esomeprazole was found to be significantly linked to CYP2C19 genotype by 11% to 29%. A mechanism-based PD model was first tested to mimic the irreversible inhibition of H(+) /K(+) -ATPase by esomeprazole using a cell-killing mechanism and models of gastric H(+) secretion that included the effects of an asymmetric circadian rhythm and food effects. Results from this PD model showed that the turnover rate of H(+) /K(+) -ATPase was significantly different between HP-negative and HP-positive subgroups. In conclusion, the PopPK model quantitatively identified the effects of the CYP2C19 genotype on esomeprazole elimination in healthy subjects for the first time. In addition, the effects of HP status on drug effect, H(+) /K(+) -ATPase turnover, and circadian rhythm amplitude were preliminarily explored using a mechanism-based PD model.

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Safety, pharmacokinetics, and pharmacodynamics of S-(−)-pantoprazole sodium injections after single and multiple intravenous doses in healthy Chinese subjects

Jiao

Sun

et al. 2017

Eur J Clin Pharmacol

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Pharmacokinetics, pharmacodynamics, and safety of esomeprazole injection/infusion in healthy Chinese volunteers: A five‐way crossover study

Abstract: Esomeprazole administrated by infusion produces better pharmacokinetic and intragastric pH profiles compared with those by injection. The optimal administration schedule for esomeprazole in Chinese subjects is infusion with 40 mg/12 h.

Cited by 6 publications

References 19 publications

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Pharmacokinetic and Pharmacodynamic Modeling Analysis of Intravenous Esomeprazole in Healthy Volunteers

Safety, pharmacokinetics, and pharmacodynamics of S-(−)-pantoprazole sodium injections after single and multiple intravenous doses in healthy Chinese subjects

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