Pharmacokinetics of the new proton pump inhibitor ilaprazole in Chinese healthy subjects in relation to CYP3A5 and CYP2C19 genotypes

Li, Yalin; Zhang, Wei; Guo, Dong; Zhang, Gan; Zhou, Hong‐Hao; Xiao, Zhousheng

doi:10.1016/j.cca.2008.02.003

Cited by 40 publications

(39 citation statements)

References 34 publications

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“…The C max of ilaprazole from Figure 4 was different from the C max and AUC determined in a previous study from our lab [4] . From the individual data, we found that the C max values of two healthy volunteers were higher than those of the other volunteers.…”

Section: Discussioncontrasting

confidence: 86%

“…The LC-MS-MS method had been reported in the literature [3,4] ; however, this is the first time that the simultaneous detection of ilaprazole, ilaprazole sulfone and ilaprazole thiol ether has been performed using this method. The C max of ilaprazole from Figure 4 was different from the C max and AUC determined in a previous study from our lab [4] .…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, our work focused on the use of liquid-liquid extraction. Hexane: ethylene chloride, MTBE, chloroform [4] , dichloromethane and ethyl acetate were evaluated as extraction solvents under neutral conditions with 100 mmol/L ammonium formate. The best recovery was observed with chloroform and MTBE as the extraction solvent.…”

Section: Extraction Methodsmentioning

confidence: 99%

“…Li et al reported that ilaprazole was metabolized by CYP3A5 and CYP2C9 in Chinese healthy subjects using a LC-MS/MS method to determine ilaprazole and ilaprazole sulfone concentrations [4] . We now report an improved LC/MS/MS method and have validated the procedure for the simultaneous detection and quantification of ilaprazole, ilaprazole sulfone and ilaprazole thiol ether in human plasma.…”

Section: Introductionmentioning

confidence: 99%

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An improved LC-MS/MS method for quantitative determination of ilaprazole and its metabolites in human plasma and its application to a pharmacokinetic study

et al. 2009

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Aim: To improve and validate an analytical method based on liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the quantitative measurement of ilaprazole and its two metablites in human plasma. Methods: Separation of analytes and the internal standard (IS), omeprazole, was performed on a Thermo HyPURITY C18 column (150×2.1 mm, 5 µm) with a mobile phase consisting of 10 mmol/L ammonium formate water-acetonitrile solution ( Results: The method was linear over the concentration range of 0.23−2400.00 ng/mL for ilaprazole, 0.05−105.00 ng/mL for ilaprazole thiol ether and 0.06−45.00 ng/mL for ilaprazole sulfone. The intra-and inter-day precisions were all less than 15% in terms of relative standard deviation (RSD), and the accuracy was within 15% in terms of relative error (RE) for ilaprazole, ilaprazole sulfone and ilaprazole thiol ether. The lower limit of quantification (LLOQ) was identifiable and reproducible at 0.23, 0.05 and 0.06 ng/mL with acceptable precision and accuracy for ilaprazole, ilaprazole sulfone and ilaprazole thiol ether, respectively. Conclusion: The validated method offered sensitivity and a wide linear concentration range. This method was successfully applied for the evaluation of the pharmacokinetics of ilaprazole and its two metabolites after single oral doses of 5 mg ilaprazole to 12 healthy Chinese volunteers.

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Section: Discussioncontrasting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Extraction Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An improved LC-MS/MS method for quantitative determination of ilaprazole and its metabolites in human plasma and its application to a pharmacokinetic study

et al. 2009

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“…[28][29][30] Accordingly, ilaprazole is expected to have a longer duration of action and less NAB compared to other PPIs. 31,32 But we found that GERD symptoms, 24-hour mean gastric pH, nocturnal mean gastric pH, frequency and duration of NAB, were comparable between the ilaprazole and omeprazole groups.…”

Section: Discussionmentioning

confidence: 99%

Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease

Karyampudi

Ghoshal

Singh

et al. 2017

J Neurogastroenterol Motil

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Background/AimsThough nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole. MethodsFifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH < 4 for > one hour during night, and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded. Results Of ConclusionsThough NAB was common while patients were on a proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole, except for the lesser number of NABs with ilaprazole.

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Identification of ilaprazole metabolites in human urine by HPLC‐ESI‐MS/MS and HPLC‐NMR experiments

Zhang

Shi

Zhang

et al. 2010

Biomedical Chromatography

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Ilaprazole is a new proton pump inhibitor designed for the treatment of gastric ulcers, and limited data is available on the metabolism of the drug. In this article, the structural elucidation of urinary metabolites of ilaprazole in human was described by HPLC-ESI-MS/MS and stopped-flow HPLC-NMR experiments. Urinary samples were precipitated by sodium carbonate solution, and then extracted by liquid-liquid extraction after adding ammonium acetate buffer solution. The enriched sample was separated using a C(18) reversed-phase column with the mobile phase composed of acetonitrile and 0.05 mol/L ammonium acetate buffer solution in a gradient solution, and then directly coupled to ESI-MS/MS detection in an on-line mode or (1)H-NMR (500 MHz) spectroscopic detection in a stopped-flow mode. As a result, four sulfide metabolites, ilaprazole sulfide (M1), 12-hydroxy-ilaprazole sulfide (M2), 11,12-dihydroxy-ilaprazole sulfide (M3) and ilaprazole sulfide A (M4), were identified by comparing their MS/MS and NMR data with those of the parent drug and available standard compounds. The main biotransformation reactions of ilaprazole were reduction and the aromatic hydroxylation of the parent drug and its relative metabolites. The result testified that HPLC-ESI-MS/MS and HPLC-NMR could be widely applied in detection and identification of novel metabolites.

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Pharmacokinetics of the new proton pump inhibitor ilaprazole in Chinese healthy subjects in relation to CYP3A5 and CYP2C19 genotypes

Cited by 40 publications

References 34 publications

An improved LC-MS/MS method for quantitative determination of ilaprazole and its metabolites in human plasma and its application to a pharmacokinetic study

An improved LC-MS/MS method for quantitative determination of ilaprazole and its metabolites in human plasma and its application to a pharmacokinetic study

Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease

Identification of ilaprazole metabolites in human urine by HPLC‐ESI‐MS/MS and HPLC‐NMR experiments

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