Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma

Tang, Chongzhuang; Liang, Li; Ma, Xiaochi; Wang, Jin; Chen, Bin; Dai, Xiaojian; Zhang, Yifan; Chen, Xiaoyan

doi:10.1016/j.jpba.2020.113146

Cited by 9 publications

(11 citation statements)

References 19 publications

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“…Among all the PPIs, rabeprazole is frequently used in clinical practice and has been verified to be a more potent repressor of H + /K + -ATPase than many other PPIs and to ensure longerlasting acid suppression and better safety performance (10,19,20). Moreover, unlike other PPIs, rabeprazole is metabolized to the thioether compound via a non-enzymatic pathway with minor involvement of cytochrome P450 (CYP) 2C19 (11,12), which is similar to anaprazole according to our preliminary study (7). Hence, we selected rabeprazole as the positive control medication in this clinical study to comparatively assess the healing efficacy of anaprazole.…”

Section: Discussionmentioning

confidence: 67%

“…The exclusion criteria were as follows: (1) patients with stress ulcers, complex ulcers, malignant ulcers or ulcers with cancerization risk; (2) patients who had esophageal erosion/ulcer, reflux esophagitis, varices of esophageal/fundus of stomach, Zollinger-Ellison syndrome; (3) patients who had severe complications, such as pyloric obstruction, active bleeding, or perforation; (4) patients with other severe gastrointestinal diseases such as active gastric ulcer or inflammatory bowel diseases; (5) patients with a history of upper gastrointestinal surgery to remove esophageal/stomach/duodenal tissue; (6) patients who failed to undergo complete endoscopies; (7) pregnant patients or those who were breastfeeding or preparing for pregnancy; (8) patients who had taken PPIs within 5 days or for over 3 consecutive days within 2 weeks prior to enrollment; (9) patients who underwent PPI-based triple/quadruple therapy for Helicobacter pylori (H. pylori) eradication within 28 days prior to enrollment; or (10) patients with consecutive use of medications inducing ulcer bleeding (e.g., steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, or antiplatelets therapy) for > 3 days within 28 days prior to enrollment.…”

Section: Patientsmentioning

confidence: 99%

“…Anaprazole [5,6-d] imidazole sodium}, a newly developed PPI with new chemical structure. In preclinical and phase I clinical trials, anaprazole has shown an equivalent half-life and pharmacodynamics to that of rabeprazole in the suppression of gastric acid secretion but has demonstrated better safety profiles with lower incidence rate of gastrointestinal adverse reaction (7). A randomized, double-blinded, placebo parallel controlled phase 1 study of multiple ascending dose administration of anaprazole in healthy Chinese subjects has investigated pharmacodynamics data (the time percentage of gastric pH value > 3 and pH value > 4 in 24 h gastric pH monitoring post dose at day 6).…”

Section: Introductionmentioning

confidence: 99%

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Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial

Shu

Zhu

et al. 2021

Front. Med.

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Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole.Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated.Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is −2.9% (95% CI, −16.5–10.7%), and −0.5% (95% CI, −13.5–12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is −1.8% (95% CI, −19.8–16.3%), and 5.1% (95% CI, −12.2–22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group.Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial.Clinical Trial Registration:https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.

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Section: Discussionmentioning

confidence: 67%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial

Shu

Zhu

et al. 2021

Front. Med.

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“…In total, the contribution of 2C19 was only 3.5%. Preclinical and phase I studies have shown that anaprazole has an equivalent half-life and pharmacodynamic profile, and an improved safety profile, compared with rabeprazole [11,12] . Patients treated with 10 mg or 20 mg rabeprazole experience high rates of ulcer healing and clinical symptom relief [13,14] .…”

Section: Introductionmentioning

confidence: 99%

“…Preclinical and phase I studies have shown that anaprazole has an equivalent half-life and pharmacodynamic profile, and an improved safety profile, compared with rabeprazole. [ 11 , 12 ] Patients treated with 10 mg or 20 mg rabeprazole experience high rates of ulcer healing and clinical symptom relief. [ 13 , 14 ] A phase II study reported similar duodenal ulcer healing rates of anaprazole and rabeprazole treatments.…”

Section: Introductionmentioning

confidence: 99%

Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study

Zhu

Xue

Zhang

et al. 2022

Chinese Medical Journal

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Background: The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori (H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods: In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint.Results: The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, À2.8% [95% confidence interval, À7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions: The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers. Registration: ClinicalTrials.gov, NCT04215653.

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Safety, Tolerability, and Pharmacokinetics of Anaprazole, a Novel Proton Pump Inhibitor, in Healthy Chinese Subjects

Wang,

Niu,

Liu

et al. 2024

Clinical Pharm in Drug Dev

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Anaprazole, a newly developed oral proton pump inhibitor, was evaluated for safety, tolerability, and pharmacokinetics in healthy Chinese subjects. This study involved administering either anaprazole sodium enteric‐coated tablet or placebo, followed by monitoring the incidence and severity of any adverse events (AEs). The pharmacokinetic parameters of anaprazole, its isomer, and main metabolisms were determined. The results showed that both single‐dose (2.5‐120 mg) and multiple‐dose (20 mg once daily, 40 mg once daily, or 20 mg twice daily) oral administration of anaprazole sodium enteric‐coated tablet were safe and well tolerated. Following single‐dose administration, the median time to reach maximum plasma concentration of anaprazole was between 3.50 and 5.25 hours, with mean elimination half‐life of 1.22‐3.79 hours. The absorption and elimination of anaprazole in the human body appeared to basically follow linear kinetics. After repeated dosing, steady‐state concentrations of anaprazole, its isomer, and primary metabolites were achieved, with a median time to reach maximum plasma concentration of 3‐3.75 hours and a mean elimination half‐life of 1.61‐2.27 hours for anaprazole. There was no significant drug accumulation after multiple‐dose oral administration. In conclusion, anaprazole sodium enteric‐coated tablets were found to be safe and well tolerated in healthy Chinese individuals. Anaprazole is absorbed and metabolized consistently in the human body without any accumulation.

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Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma

Cited by 9 publications

References 19 publications

Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial

Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial

Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study

Safety, Tolerability, and Pharmacokinetics of Anaprazole, a Novel Proton Pump Inhibitor, in Healthy Chinese Subjects

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