Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects

Sun, Liang; Cao, Yang; Li, Yue-Qi; Fang, Yunqian; Zhang, Hongwen; Wang, Meifeng; Xie, Ling; Chen, Juan; Yang, Zhicheng; Bian, Ming-Liang; Li, Hao; Zhang, Peipei; Wei, Ji‐Fu; Meng, Ling; Zhang, Xuehui; Zhao, Ping; Wang, Yongqing

doi:10.3389/fphar.2017.00670

Cited by 9 publications

(13 citation statements)

References 33 publications

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“…There are fewer data available investigating the association between dexlansoprazole and CYP2C19 metabolizer status compared with the first‐generation PPIs. However, reported pharmacokinetic data support the association between CYP2C19 IMs and PMs and increased dexlansoprazole exposure 13,27 . Additionally, CYP2C19 PMs were reported to have greater acid suppression compared with NMs 13 .…”

Section: Drugs: Proton Pump Inhibitorsmentioning

confidence: 88%

“…However, reported pharmacokinetic data support the association between CYP2C19 IMs and PMs and increased dexlansoprazole exposure. 13,27 Additionally, CYP2C19 PMs were reported to have greater acid suppression compared with NMs. 13 Given the similarity in metabolism between lansoprazole and dexlansoprazole, it is reasonable to extrapolate the recommendations from the first-generation PPIs (Table 2).…”

Section: Cpic Guidelinementioning

confidence: 99%

“…13,27 Additionally, CYP2C19 PMs were reported to have greater acid suppression compared with NMs. 13 Given the similarity in metabolism between lansoprazole and dexlansoprazole, it is reasonable to extrapolate the recommendations from the first-generation PPIs (Table 2). These recommendations are considered "optional" due to the limited data with dexlansoprazole and CYP2C19.…”

Section: Cpic Guidelinementioning

confidence: 99%

“…As outlined in TableS4-S6, the evidence associating CYP2C19 genotype with esomeprazole, rabeprazole, and dexlansoprazole plasma concentrations, efficacy, and toxicity was graded as moderate or weak. While fewer data exist on the influence of CYP2C19 genotype on dexlansoprazole compared with first-generation PPIs, similar effects of CYP2C19 genotype on dexlansoprazole pharmacokinetics and effectiveness are expected given its similar metabolic pathway to lansoprazole 1,13. Inconsistent findings regarding the effect of CYP2C19 genotype on the pharmacokinetics and therapeutic response to esomeprazole and rabeprazole preclude making recommendations for these second-generation PPIs (i.e., CPIC level C; no recommendation).…”

mentioning

confidence: 99%

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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing

Lima

Thomas

Barbarino

et al. 2020

Clin Pharma and Therapeutics

206

207

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Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at http://www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long‐term PPI use, particularly at higher plasma concentrations.

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Section: Drugs: Proton Pump Inhibitorsmentioning

confidence: 88%

Section: Cpic Guidelinementioning

confidence: 99%

Section: Cpic Guidelinementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing

Lima

Thomas

Barbarino

et al. 2020

Clin Pharma and Therapeutics

206

207

View full text Add to dashboard Cite

show abstract

“…To date, a few studies have been conducted providing the evidence for controlling intragastric pH after intravenous infusion of dexlansoprazole developed by other pharmaceutical companies, but the original injection preparation of lansoprazole has never been used in these studies, and no clearly improved acid inhibition profile was noted [11, 12].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Evaluation of Dexlansoprazole Infusion Injection Compared with Lansoprazole in Healthy Chinese Adults

Liu

Zheng

et al. 2019

Clin Drug Investig

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Background and ObjectiveThis study was performed in healthy Chinese subjects to evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of a novel injection formulation of dexlansoprazole in the context of single and multiple administration, compared with the original lansoprazole injection.MethodsHelicobacter pylori-negative healthy volunteers were recruited, and 70 participants were enrolled into five dosing groups (seven males and seven females in each group), including 15 mg once daily (qd), 15 mg every 12 h (q12h), 30 mg qd and 30 mg q12h of dexlansoprazole treatment for 5 days, as well as 30 mg q12h of lansoprazole treatment for 5 days. Blood samples were collected at scheduled time spots postdose on day 1 (first dose) and day 5 (last dose). Twenty-four-hour intragastric pH was continuously monitored on day 0 (baseline) and days 1 and 5. Dexlansoprazole and S-lansoprazole in human plasma were determined by validated chiral liquid chromatography with tandem mass spectrometry, and the pharmacokinetic parameters were determined by a non-compartmental method using Phoenix WinNonlin software. Safety assessment included changes in vital signs and laboratory tests, physical examination findings, and incidence or reports of adverse events.ResultsThe half-life (t½) and clearance (CL) of dexlansoprazole were 1.76–2.06 h and 4.52–5.40 L/h, respectively, while the t½ and CL of S-lansoprazole were 0.87–1.02 h and 34.66–35.98 L/h, respectively. No drug accumulation after repeated administration was noted. Administration of lansoprazole 30 mg resulted in higher area under the concentration-time curve from time zero to the last measurable concentration (AUCt) of dexlansoprazole than that of dexlansoprazole 15 mg (p = 0.026). Zero to 24 h after q12h multiple dosing, median and mean intragastric pH, percentage of time with the intragastric pH above 4.0 [TpH ≥ 4.0(%)] and percentage of time with the intragastric pH above 6.0 [TpH ≥ 6.0(%)] in the dexlansoprazole 15 mg q12h group were 6.07 ± 0.61, 5.70 ± 0.76, 83.58 ± 12.34, and 53.70 ± 17.06, respectively, which was similar to the lansoprazole 30 mg q12h group, i.e. 6.15 ± 0.62, 5.88 ± 0.67, 87.26 ± 12.08 and 57.00 ± 16.35, respectively. A weak positive correlation between dexlansoprazole AUCt and baseline-adjusted TpH ≥ 4.0(%) over 0–24 h was observed, with Pearson correlation coefficients of 0.437 (p = 0.029), while no correlation was observed between AUCt and baseline-adjusted TpH ≥ 6.0(%) over 0–24 h.ConclusionEvery 12 h intravenous dosing of dexlansoprazole up to 30 mg for 5 days was safe and well-tolerated in healthy Chinese subjects. Every 12 h dosing of dexlansoprazole 15 mg has a comparable effect of gastric acid inhibition as lansoprazole 30 mg q12h.Trial RegistrationClinicalTrials.gov ID NCT03120273.

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Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors

Zhang

Liu

et al. 2020

Pharmacological Research

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Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects

Cited by 9 publications

References 33 publications

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing

Pharmacokinetic/Pharmacodynamic Evaluation of Dexlansoprazole Infusion Injection Compared with Lansoprazole in Healthy Chinese Adults

Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors

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