Cost-effectiveness analysis of Anaprazole versus Ilaprazole for the treatment of duodenal ulcers in China.

Objective: Anaprazole, an innovative drug, has shown promise in initial clinical trials for patients with duodenal ulcers (DU) in China. This study aimed to evaluate the potential effects, safety, and cost-effectiveness of Anaprazole compared to Ilaprazole in the treatment of DU and the budgetary impact on the healthcare system. Methods: Two multicentre, randomized controlled trials were used as data sources. The efficacy and safety of Anaprazole and Ilaprazole were compared using an anchored matching-adjusted indirect comparison (MAIC). A cost-utility analysis (CUA) was performed using a Markov model. A budget impact analysis (BIA) was conducted to evaluate the impact on the expenditure of the Chinese healthcare system. Deterministic and probabilistic sensitivity analyses were undertaken to test the uncertainty. Results: The study findings indicated that Anaprazole and Ilaprazole have similar efficacy and safety in treating DU (OR = 1.05; 95% CI, 0.94-1.01; p = 0.35; OR = 0.63; 95% CI, 0.39-1.08; p = 0.12). The ICUR was 2,995.41¥/QALY, which is below the WTP threshold. The CUA results showed that Anaprazole is a cost-effective intervention with a probability of 85% at a given threshold. The results demonstrated strong robustness in the sensitivity analysis. Anaprazole imposed a low burden on the Chinese healthcare budget in the BIA. Conclusion: Compared with Ilaprazole, Anaprazole has similar efficacy, safety, and high cost-effectiveness, while also impacting the total expenditure of the healthcare system. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04215653 and NCT02847455.

Computational drug-drug interaction prediction mediated by CYP450 isoforms of Ilaprazole coadministered with clopidogrel.

Ilaprazole due to its pharmacokinetic variability does not affect the clopidogrel efficacy during concomitant use. Methodology: Prediction of DDI for Clopidogrel and PPIs performed using (DDI-Pred) Way2Drug software. The probabilities ΔP, which estimate the potential DDIs resulting from interaction with CYP450 isoenzymes. Results: Positive ΔP-values for CYP2C19 (0.955) indicate that it is involved in the drug interaction of Ilaprazole and Clopidogrel. Discussion: Pantoprazole and Ilaprazole were found to have a low probability of CYP2C19 inhibition Conclusion: Compared with other PPIs, Pantoprazole and Ilaprazole were found to have a low probability of CYP2C19 inhibition; Since Ilaprazole has pharmacokinetic variability, further in vivo and in vitro studies are required on the ilaprazole and clopidogrel combination to assess the effect of drug-drug interaction.

Investigation of the Storage and Stability as Well as the Dissolution Rate of Novel Ilaprazole/Xylitol Cocrystal.

Reflux esophagitis, a treatment for gastric ulcers known as Ilaprazole (Ila), is not stable during storage and handling at room temperature, requiring storage at 5 degrees Celsius. In this study, to address these issues with Ila, coformers rich in oxygen (O) and hydroxyl (OH) groups capable of forming hydrogen bonds with were selected. These coformers included Xylitol (Xyl), Meglumine (Meg), Nicotinic acid (Nic), L-Aspartic acid (Asp), and L-Glutamic acid (Glu). A 1:1 physical mixture of Ila and each coformer was prepared, and the potential for cocrystal formation was predicted using differential scanning calorimetry (DSC) screening. The results indicated the potential for cocrystal formation in the Ila/Xyl physical mixture. Subsequently, Ila and Xyl were mixed in ethyl acetate (EA) in a 1:1 ratio, and after 28 h of slurry, the formation of Ila/Xyl cocrystal was confirmed through solid-state CP/MAS 13C NMR spectrum analysis, showing intermolecular hydrogen bonding and conformational changes. Furthermore, the 1:1 ratio of Ila/Xyl cocrystal was confirmed through solution-state NMR (1H, 13C, and 2D) molecular structure analysis. To assess the stability of Ila/Xyl cocrystal at room temperature, it was stored and compared with Ila at 25 ± 2 °C and relative humidity (RH) of 65 ± 5% over three months. The results showed that the purity of Ila/Xyl cocrystal remained at 99.8% from the initial purity of 99.75% over the three months, while Ila was predicted to decrease from an initial 99.8% purity to 90% after three months. Additionally, at 25 ± 2 °C and RH 65 ± 5%, a specific impurity B in Ila/Xyl cocrystal was observed to be 0.03% over three months, whereas Ila was predicted to increase from an initial 0.032% to 2.28% after three months. To evaluate the dissolution rate of Ila/Xyl cocrystal, a formulation was prepared and compared with Ila at pH 10, with a dosage equivalent to 10 mg of Ila. The results showed that Ila/Xyl cocrystal reached 55% within 15 min and 100% within 45 min, while Ila was predicted to reach 32% at 15 min and 100% only after 60 min. However, overall, the Ila/Xyl cocrystal showed results equivalent to or exceeding the dissolution rate of Ila. Therefore, it is predicted that the Ila/Xyl cocrystal will maximize its effectiveness as a more convenient crystal structure for formulation development, allowing storage and preservation at room temperature without the need for the problematic 5 °C refrigeration during ambient conditions and storage, addressing the issues associated with Ila.

Efficacy and safety of high-dose ilaprazole-amoxicillin dual therapy for Helicobacter pylori eradication: a prospective, single-center, randomized trial.

Background: Until now, there have been no randomized controlled trials directly evaluating the efficacy of high-dose ilaprazole-amoxicillin dual therapy (HT) in comparison to other standard treatments for H. pylori (Helicobacter pylori) infection. This study aimed to compare the effectiveness and safety of HT with bismuth quadruple therapy (BQT) as an initial treatment for H. pylori. Methods: This single-center, prospective, randomized clinical controlled trial recruited 225 consecutive patients. They were assigned to either HT group (ilaprazole, 10 mg, twice daily; amoxicillin 1,000 mg, three times daily) or BQT group (compound bismuth aluminate granules, 2.6 g, three times daily; ilaprazole, 5 mg, twice daily; amoxicillin, 1,000 mg, twice daily; clarithromycin, 500 mg, twice daily) for 14 days. The 13C-urea breath test assessed eradication success 4 weeks after treatment. The primary outcome focused on the eradication rate, with secondary outcomes including safety and compliance. Results: From February 2023 to March 2023, 228 subjects were screened, and 225 were randomized. The HT and BQT groups showed eradication rates of 76.3% and 61.3% (p = 0.015) both by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. HT was associated with fewer adverse events than BQT (27.2% vs. 81.8%, p = 0.002). The most commonly reported adverse events was bitter taste of mouth (3.5% vs. 60.4%, p < 0.001). There was no significant difference in compliance between the two groups (89.5% vs. 92.8%, p = 0.264). Conclusion: The 14-day HT treatment demonstrates better efficacy in H. pylori eradication treatment and improved safety and compliance compared to BQT. The results provide supporting evidence for 14-day HT can be potentially considered as a first-line regimen for empirical treatment. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=186562, identifier ChiCTR2200066284.

Ilaprazole-amoxicillin dual therapy at high dose as a first-line treatment for helicobacter pylori infection in Hainan: a single-center, open-label, noninferiority, randomized controlled trial.

OBJECTIVES: This study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients. METHODS: 200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4-6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups. RESULTS: Eradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B. CONCLUSIONS: IA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

Population pharmacokinetic modeling of ilaprazole in healthy subjects and patients with duodenal ulcer in China.

Aims: This study aimed to develop a population pharmacokinetic (PopPK) model of ilaprazole in healthy subjects and patients with duodenal ulcer in Chinese and investigate the effect of potential covariates on pharmacokinetic (PK) parameters. Methods: Pharmacokinetic data from 4 phase I clinical trials and 1 phase IIa clinical trial of ilaprazole were included in PopPK analysis. Phoenix NLME 8.3 was used to establish a PopPK model and quantify the effects of covariate, such as demographic data, biochemical indicators and disease state on the PK parameters of ilaprazole. The final model was evaluated by goodness-of-fit plots, bootstrap analysis, and visual predictive check. Results: A two-compartment model with first-order elimination successfully described the pharmacokinetic properties of ilaprazole. In the final PopPK model, body weight and sex were identified as statistically significant covariates for volume of peripheral compartment (Vp) and clearance of central compartment (CL), respectively, and disease status was also screened as a significant covariate affecting both CL and Vp. The validation results demonstrated the good predictability of the model, which was accurate and reliable. Conclusion: This is the first population pharmacokinetics study of ilaprazole in the Chinese, and the PopPK model developed in this study is expected to be helpful in providing relevant PK parameters and covariates information for further studies of ilaprazole.

Meta-analysis of the efficacy and safety of Ilaprazole Enteric-Coated Tablets on reflux esophagitis / 药学实践杂志

Objective To evaluate the efficacy and safety of Ilaprazole Enteric-Coated Tablets in the treatment of RE. Methods The databases of CNKI, VIP, Wanfang Data, PubMed, Embase, and The Cochrane Library were searched to collect all the randomized controlled trials (RCTs) of Ilaprazole in the treatment of RE published before April 2021. After data extraction and quality evaluation, the RCTs meeting the inclusion criteria were performed, and the meta-analysis was conducted by RevMan 5.4. Results Nine RCTs were included, with a total of 1115 patients of RE. The results of the meta-analysis showed that Ilaprazole Enteric-Coated Tablets were comparable to Esomeprazole Enteric-Coated Tablets in both endoscopic efficiency (90.08% vs. 90.00%, P > 0.05) and symptom relief rates (91.79% vs. 91.23%, P > 0.05), and there was no statistically significant difference in the incidence of adverse reactions (7.99% vs. 8.66%, P > 0.05). Conclusion Ilaprazole Enteric-Coated Tablets with lower doses were comparable to Esomeprazole Enteric-Coated Tablets which showed good efficacy and safety in the treatment of reflux esophagitis.

Retrospective multicenter nested case-control safety study of Ilaprazole sodium for injection / 中国药房

OBJECTIVE To understand the safety of Ilaprazole sodium for injection in clinical practice. METHODS From Jan. 1st 2019 to Feb. 29th 2020， the data of 3 926 valid hospitalized patients receiving Ilaprazole sodium for injection were collected prospectively from 5 third-level hospitals through CHPS， and the post-marketing safety analysis was performed by using retrospective multicenter single cohort study. At the same time， a nested case-control study （the ratio of trial group and control group was 1∶4） was used to confirm the baseline stability of this study cohort and the correlation between adverse reactions and Ilaprazole sodium for injection. RESULTS Among 3 926 patients， 3 patients experienced 5 adverse drug events after using Ilaprazole sodium for injection， with the incidence of 0.076%. There was no serious adverse event， and the occurrence time was 2 days after medication； adverse drug events mainly include elevated liver function indicators （alanine transaminase， aspartate transaminase， total bilirubin）， which were mild and untreated， and all adverse drug events were improved. The results of the nested case-control study showed that the trial group and the control group belonged to the same background baseline， and the occurrence of adverse drug events was more closely related to Ilaprazole sodium for injection. CONCLUSIONS The overall safety of Ilaprazole sodium for injection is relatively high， and the occurrence of adverse events is more related to it.

Effects of ilaprazole on the steady-state pharmacodynamics of clopidogrel in healthy volunteers: An open-label randomized crossover study.

Background: Previous studies have suggested that proton pump inhibitors could impair the antiplatelet effect of clopidogrel. It is uncertain whether ilaprazole affects the antiplatelet effect of clopidogrel. This study aimed to determine the drug-drug interaction between ilaprazole and clopidogrel. Methods: A randomized crossover trial of 40 healthy subjects was performed. Clopidogrel was administered alone or in combination with ilaprazole for 7 days. The maximal platelet aggregation (MPA) to 5 µmol/L adenosine diphosphate was measured by light transmission aggregometry and the platelet reactivity index (PRI) was determined by vasodilator-stimulated phosphoprotein P2Y12 assay. High on-treatment platelet reactivity (HOPR) was defined as a MPA of >40%. The inhibition of platelet aggregation (IPA) and PRI in the two phases were compared between two regimens after the last dosing. Results: IPA was comparable between the two regimens at 0, 10 and 24 h (p > 0.05), but higher at 4 h in the clopidogrel alone regimen compared with that in the combined treatment regimen (75.66 ± 18.44% vs. 70.18 ± 17.67%, p = 0.031). The inhibition of PRI was comparable between the two regimens at 0 and 24 h. There were no significant differences in the area under the time-IPA% curve (AUC) or the incidence of HOPR at all time-points between the two regimens. Conclusion: In healthy subjects, ilaprazole has limited effect on the pharmacodynamics of clopidogrel and it may not be clinically relevant. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2000031482].

Ilaprazole and Clopidogrel Resistance in Acute Stroke Patients.

Clopidogrel, an antiplatelet agent used for secondary prevention of cerebrovascular diseases, is often taken with proton pump inhibitors (PPIs). Generally, the combined use of clopidogrel and PPIs causes adverse drug-drug interactions. VerifyNow is a quick and convenient method to confirm clopidogrel resistance (CR), which compromises adequate antithrombotic effects. We aimed to confirm CR, identify its factors, and determine the influence of the combination of ilaprazole and clopidogrel on clopidogrel using VerifyNow. In this retrospective study, we examined patients who were receiving clopidogrel after three months, starting within one week from the onset of cerebral infarction symptoms. Clinical records, imaging records, and diagnostic laboratory results, including P2Y12 reaction units (PRU), were compared and analyzed to check for CR. Additionally, the groups treated with either both ilaprazole and clopidogrel or with medications other than ilaprazole were comparatively analyzed. CR was defined as a PRU ≥240 after clopidogrel for three months. Among factors influencing CR by affecting clopidogrel metabolism, positive statistical correlations with age and alcohol consumption were confirmed. The diagnostic tests revealed a lower glomerular filtration rate and platelet count of the CR-positive group. This finding proved that the combination therapy of ilaprazole and clopidogrel is safe, as it does not interfere with the metabolism of clopidogrel.

Improved motility in the gastrointestinal tract of a postoperative ileus rat model with ilaprazole.

Postoperative ileus (POI), a symptom that occurs after abdominal surgery, reduces gastrointestinal motility. Although its mechanism is unclear, POI symptoms are known to be caused by inflammation 6 to 72 h after surgery. As proton pump inhibitors exhibit protective effect against acute inflammation, the purpose of this study was to determine the effect of ilaprazole on a POI rat model. POI was induced in rats by abdominal surgery. Rats were divided into six groups: control: normal rat + 0.5% CMC-Na, vehicle: POI rat + 0.5% CMC-Na, mosapride: POI rat + mosapride 2 mg/kg, ilaprazole 1 mg/kg: POI rat + ilaprazole 1 mg/kg, ilaprazole 3 mg/kg: POI rat + ilaprazole 3 mg/kg, and ilaprazole 10 mg/kg: POI rat + ilaprazole 10 mg/kg. Gastrointestinal motility was confirmed by measuring gastric emptying (GE) and gastrointestinal transit (GIT). In the small intestine, inflammation was confirmed by measuring TNF-α and IL-1ß; oxidative stress was confirmed by SOD, GSH, and MDA levels; and histological changes were observed by H&E staining. Based on the findings, GE and GIT were decreased in the vehicle group and improved in the ilaprazole 10 mg/kg group. In the ilaprazole 10 mg/kg group, TNF-α and IL-1ß levels were decreased, SOD and GSH levels were increased, and MDA levels were decreased. Histological damage was also reduced in the ilaprazole-treated groups. These findings suggest that ilaprazole prevents the decrease in gastrointestinal motility, a major symptom of postoperative ileus, and reduces inflammation and oxidative stress.

Accelerating Development of Benziamidazole-Class Proton Pump Inhibitors: A Mechanism-Based PK/PD Model to Optimize Study Design with Ilaprazole as a Case Drug.

Proton pump inhibitors (PPIs) are the mainstay for treatment of acid-related diseases. This study developed a mechanism-based pharmacokinetic (PK) and pharmacodynamics (PD) model with ilaprazole as case drug, so as to support and accelerate the development of novel PPIs. The model was established and verified using the PK and PD data from 26 subjects receiving 5 to 30 mg of ilaprazole and 22 subjects receiving the loading dose of ilaprazole 20 mg followed by 10 mg once daily for 2 days. The nonlinear mixed-effects modeling approach was performed for the PK/PD model. A two-compartment model with linear elimination and covariates (body weight and gender) described the observed data well. The relationship between plasma concentrations of ilaprazole and gastric acid pH was well quantified with individual variability, in which the synthesis and degradation of H+/K+-ATPase, the food effect, the circular rhythms of gastric acid secretion, and the irreversible inhibition of H+/K+-ATPase by ilaprazole were integrated. This PK/PD model well predicted the PK and PD profile of ilaprazole in healthy subjects and patients with duodenal ulcers receiving wide range dose regimens. The mechanism-based PK/PD model provided a potential strategy to accelerate the development of novel PPIs by waiving the unnecessary clinical trials.

Identification of the New In Vivo Metabolites of Ilaprazole in Rat Plasma after Oral Administration by LC-MS: In Silico Prediction of the H+/K+-ATPase Inhibitor.

Ilaprazole is a proton pump inhibitor used to treat digestive diseases. In this study, blood samples were collected after oral administration of ilaprazole and prepared by liquid-liquid extraction. The metabolites of ilaprazole were detected by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and LC-MSn. A total of twelve in vivo metabolites were detected in rat plasma and six new metabolites of ilaprazole, including one reductive metabolite with sulfide (M3), two hydroxylated metabolites with sulfoxide (M7 and M8), and three oxidative metabolites with sulfone (M9, M11, and M12), were identified. The possible metabolic pathways of ilaprazole and the fragmentation behaviors of its metabolites were elucidated. The result of the in silico prediction indicates that all the new metabolites showed the potential ability to inhibit H+/K+-ATPase activity.

The controlled study of efficacy and safety of infusion of ilaprazole sodium versus esomeprazole sodium in prevention of peptic ulcer rebleeding / 中华消化杂志

Objective:To explore the efficacy and safety of intermittent infusion of ilaprazole sodium and high-dose continuous infusion of esomeprazole sodium in preventing rebleeding in patients with peptic ulcer bleeding after successful endoscopic hemostasis.Methods:This is a multi-center, interval randomized, double-blind, double-dummy, parallel controlled study. From March 3rd to June 15th, 2021, 151 patients with high risk of peptic ulcer bleeding and successfully underwent endoscopic hemostasis from 33 hospitals including the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Patients were interval randomly divided into the trial group (74 cases) and the control group (77 cases). Patients in the trial group received intermittent intravenous infusion of ilaprazole sodium once daily (20 mg administered as a 60 min intravenous infusion on day 1, and 10 mg administered as a 30 min intravenous infusion on day 2 and 3); patients in the control group received continuous intravenous infusion of esomeprazole sodium for 72 h (esomeprazole sodium 80 mg at first dose in half an hour, and 8 mg per hour continuous intravenous infusion for 71.5 h). After intravenous infusion treatment, patients of both groups were given oral ilaprazole enteric-coated tablets, 10 mg each time, once a day for 4 d. The rebleeding rate after 72 h and within 7 d after treatment and the proportion of patients who received endoscopic retreatment or surgery due to rebleeding within 72 h after treatment were analysised based on the full analysis set (72 cases in the trial group and 75 cases in the control group); and the incidence rate of adverse reactions was observed in the two groups based on the safety analysis set (74 cases in the trial group and 76 cases in the control group). Chi-square test or Fisher exact probability test was used for statistical analysis.Results:There was no rebleeding case in the trial group within 72 h and 1 case of rebleeding within 7 d (1.39%, 1/72). In the control group, there was 1 case of rebleeding (1.33%, 1/75) within 72 h and 4 cases of rebleeding (5.33%, 4/75) within 7 d. There was no significant difference in rebleeding rate either after 72 h or within 7 d after treatment between the two groups (both P>0.05). Within 72 h of treatment, no patients in both groups needed endoscopic or surgical retreatment due to rebleeding. Adverse reactions occurred in 5 cases (6.8%, 5/74) and 6 cases (7.9%, 6/76) in the trial group and control group, respectively, which recovered spontaneously without treatment. No serious adverse reactions occurred in both groups. Conclusion:In patients with high-risk peptic ulcer bleeding with successful endoscopic hemostasis, intermittent intravenous infusion of ilaprazole sodium has similar efficacy and safety as continuous high-dose intravenous infusion of esomeprazole sodium, but the dosage of intermitten regimen is less, the administration is more convenient, and it is worthy of clinical promotion.

The study of intestinal absorption and biodistribution in vivo of proton pump inhibitors.

The major therapeutic strategy for acid-related gastrointestinal diseases in clinic is to reduce the excretion of gastric acid by oral administration of proton-pump inhibitors (PPIs). However, it is quite a challenge to study the oral absorption behaviors of PPIs considering their extreme instability under gastrointestinal environment. As a result, little information has been reported on PPI oral absorption so far, hindering the further development of PPI-contained oral preparations. Here, we first investigated the degradation rate of three representative PPIs, including ilaprazole, ilaprazole sodium and rabeprazole sodium. Then a modified in situ intestine absorption method in rat was established: through the temperature control by the heat exchangers, the perfusate was kept at physiological temperature only when passing through the intestine while it was maintained at 4 °C outside the intestine. Therefore PPIs could maintained sufficiently high stability under proper temperature control. Our data demonstrated that both ilaprazole and ilaprazole sodium exhibited significantly higher absorption efficiency than rabeprazole sodium did through the comparison of their apparent permeability coefficients and steady-state plasma concentrations after perfusion in the duodenum, jejunum, ileum and colon, mainly attributing to their more suitable oil-water partition coefficient. The duodenum could be the best site for the oral absorption of PPIs. Ilaprazole outperformed its sodium salt form with its stable absorption behavior in tested four intestinal segments. Furthermore, after intravenous or oral administration, ilaprazole exhibited a longer residence time and a higher accumulation in the stomach than in most of other tissues/organs. However, it was also found that the accumulation was heterogeneous and mainly located in mucosa cells of the stomach. Our further study indicated that there was no significant difference on the oral absorption efficiency of ilaprazole between female and male rats but ilaprazole underwent a faster metabolism in male rats after oral absorption. Our study provided a valuable guidance for the design of oral formulation and the optimization of PPI-contained formulations.

Development of a UHPLC-MS/MS method for the quantification of ilaprazole enantiomers in rat plasma and its pharmacokinetic application.

In Korea and China, ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers. In this study, a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma, using R-lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.6 mm × 150 mm, i.d. 5 µm), with a mobile phase composed of 10 mM ammonium acetate aqueous solution and acetonitrile (60:40, V/V), at a flow-rate of 0.5 mL/min. The method was validated over the concentration range of 0.5-300 ng/mL for both, R- and S -ilaprazole. The lower limit of quantification was 0.5 ng/mL for both enantiomers. The relative standard deviation (RSD) of intra- and inter-day precision of R-ilaprazole and S-ilaprazole was less than 10.9%, and the relative error accuracy (RE) ranged from -0.5%-2.0%. Finally, the method was successfully evaluated in rats in a stereoselective pharmacokinetic study of the ilaprazole racemate.

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

Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H+,K+-ATPase and CYP2C19 polymorphisms, although gastric H+,K+-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture.

Development of a UHPLC-MS/MS method for the quantification of ilaprazole enantiomers in rat plasma and its pharmacokinetic application / 药物分析学报

In Korea and China, ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers. In this study, a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma, using R-lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.6 mm × 150 mm, i.d. 5μm), with a mobile phase composed of 10 mM ammonium acetate aqueous solution and acetonitrile (60:40, V/V), at a flow-rate of 0.5 mL/min. The method was validated over the concentration range of 0.5-300 ng/mL for both, R- and S -ilaprazole. The lower limit of quantification was 0.5 ng/mL for both enantiomers. The relative standard deviation (RSD) of intra- and inter-day precision of R-ilaprazole and S-ilaprazole was less than 10.9％, and the relative error accuracy (RE) ranged from -0.5％-2.0％. Finally, the method was successfully evaluated in rats in a stereoselective pharmacokinetic study of the ilaprazole racemate.

Ilaprazole Enteric-coated Tablets in the Treatment of Duodenal Ulcer:A Rapid Health Technology Assessment / 中国药学杂志

OBJECTIVE: To rapidly evaluate the efficacy, safety and economical efficiency of ilaprazole enteric-coated tablets in the treatment of duodenal ulcer, so as to provide evidence-based evidence for clinical rational drug use. METHODS: PubMed, Embase, the Cochrane Library, CNKI, WanFang database and health technology assessment (HTA) organization websites were searched systematically. HTA reports, systematic reviews/Meta-analysis and pharmacoeconomic studies comparing ilaprazole with other drugs for duodenal ulcer treatment were included. Qualitative and descriptive analysis were performed on the included studies. RESULTS: A total of 10 literatures were included, including five systematic reviews/Meta-analysis and six pharmacoeconomic research (one systematic reviews/Meta-analysis also carried out pharmacoeconomic research). The efficacy of ilaprazole (10 mg•d-1) was comparable to other PPIs regimens in the treatment of duodenal ulcer, and there was no statistically significant difference in the efficacy of ilaprazole (10 mg•d-1) and ilaprazole (5 mg•d-1). Compared with H2 receptor antagonists, ilaprazole (10 mg•d-1) was significantly better than ranitidine and famotidine in the treatment of duodenal ulcer. In terms of safety, there was no statistical difference in the incidence of adverse reactions between ilaprazole (10 mg•d-1) and other PPIs or H2 receptor antagonists. In terms of the economics of treating duodenal ulcer, ilaprazole (10 mg•d-1) was not economical compared to esmeprazole (40 mg•d-1), while ilaprazole (5 mg•d-1) was more economical than rabeprazole (10 mg•d-1). CONCLUSION: Ilaprazole enteric-coated tablets are safe and effective in the treatment of duodenal ulcer, not inferior to other PPIs, and have economic advantages compared with rabeprazole. Because ilaprazole (10 mg•d-1) and ilaprazole (5 mg•d-1) have comparable efficacy, a low-dose regimen could be considered clinically to further improve its safety and cost performance. At the same time, it is necessary to further carry out clinical and pharmacoeconomic studies of low-dose ilaprazole in the treatment of duodenal ulcer to improve the relevant evidence.

Efficacy, safety and pharmacokinetics of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control.

AIMS: The objectives were to investigate the pharmacokinetics, pharmacodynamics and safety of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control, and then recommend the dosage regimen for Phase 2b/3 studies. METHODS: Three clinical studies were performed. First, 16 healthy subjects received infusion of ilaprazole 30 mg or esomeprazole 80 mg. Second, 12 healthy subjects received ilaprazole 20 mg followed by 10 mg once daily for 2 days. Finally, 20 patients with duodenal ulcers received ilaprazole 20 mg followed by 10 mg for 2 days or esomeprazole 40 mg twice daily for 3 days. Serial blood samples were collected and intragastric pH was recorded. RESULTS: The mean percentages time of intragastric pH >6 was 63.6 and 51.7% for healthy subjects after receiving ilaprazole 30 mg and esomeprazole 80 mg. Linear pharmacokinetics was observed when the dose was increased to 30 mg but the effect was saturated. Ilaprazole 20 mg followed by 10 mg for 2 days provided higher plasma exposure in healthy subjects than patients, but the effect was comparable. After multiple administrations, ilaprazole provided similar effect to esomeprazole. Ilaprazole infusion was safe and well tolerated without serious adverse events. CONCLUSIONS: Ilaprazole provided comparable effect of pH control to esomeprazole, with lower dose and fewer times of administration. There was no significant difference of ilaprazole between healthy subjects and patients regarding intragastric acid inhibition. A loading dose of ilaprazole 20 mg followed by 10 mg once daily for 2 days was recommended for Phase 2b/3 studies.