s-1743 and omeprazole-sulfone

s-1743 has been researched along with omeprazole-sulfone* in 3 studies

Trials

1 trial(s) available for s-1743 and omeprazole-sulfone

ArticleYear
Esomeprazole-induced healing of gastroesophageal reflux disease is unrelated to the genotype of CYP2C19: evidence from clinical and pharmacokinetic data.
    Clinical pharmacology and therapeutics, 2005, Volume: 78, Issue:6

    The clinical outcome of acid-related disorders treated by proton pump inhibitors (PPIs) might be dependent on the polymorphically expressed cytochrome P450 (CYP) 2C19, which is involved in PPI metabolism. We tested whether esomeprazole-induced healing of gastroesophageal reflux disease (GERD) is related to CYP2C19 genotype.. Two hundred five patients with GERD (Los Angeles classification grade A or B) were included in a case-control study according to endoscopic outcome (healed versus unhealed group, matched for confounders) after treatment with 40 mg esomeprazole daily for 4 weeks. The frequency of CYP2C19 genotypes was determined as the primary outcome measure for both groups. In a second trial plasma levels of esomeprazole and corresponding CYP2C19 and CYP3A4 metabolites (5-hydroxyomeprazole and omeprazole sulfone) were monitored in 10 CYP2C19 wild-type patients with GERD after the first and last doses (day 7) of 40 mg esomeprazole daily to calculate metabolic ratios.. CYP2C19 wild-type (n = 148) and heterozygous (n = 51) or homozygous variant (n = 6) patients did not differ with respect to baseline characteristics. The frequency distribution of CYP2C19 genotypes was not different between patients with complete (75/100) and incomplete (73/105) healing (P = .65). When a single esomeprazole dose and multiple dosing were compared, the low contribution of CYP2C19 to the elimination of esomeprazole decreased further by 50%. In contrast, the CYP3A4-dependent formation of omeprazole sulfone increased by 40%, and consequently, the metabolic ratio of omeprazole sulfone to 5-hydroxyomeprazole was elevated from 7.9 to 19.3 (P = .0004).. In contrast to other PPIs, esomeprazole-induced healing of GERD is unrelated to the CYP2C19 genotype, which can be explained by the metabolic shift toward the CYP3A4-mediated pathway.

    Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Aged; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Case-Control Studies; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Genotype; H(+)-K(+)-Exchanging ATPase; Half-Life; Humans; Male; Middle Aged; Mixed Function Oxygenases; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Time Factors

2005

Other Studies

2 other study(ies) available for s-1743 and omeprazole-sulfone

ArticleYear
Development and validation of a DESI-HRMS/MS method for the fast profiling of esomeprazole and its metabolites in rat plasma: a pharmacokinetic study.
    Drug testing and analysis, 2016, Volume: 8, Issue:2

    The advances in pharmaceutical development and drug discovery impose the availability of reliable high-throughput screening methods for the rapid evaluation of drug metabolism and pharmacokinetic (PK) in biological samples. Here, a desorption electrospray mass spectrometry (DESI-MS) method has been developed and validated for the PK profiling of esomeprazole and its metabolites (5-hydroxyomeprazole and omeprazole sulfone) in rat plasma. Rats were treated with an esomeprazole solution (2.5 mg/mL) for endovenous administration and the analyte levels were profiled over 2 h after liquid-liquid extraction from plasma. MS and tandem mass spectrometry (MS/MS) experiments were performed by using a DESI-LTQ-Orbitrap XL instrument and an on-spot fixed time analysis on PMMA surfaces. Validation was performed for the esomeprazole. The DESI-MS/MS method exhibited for the esomepazole excellent sensitivity (limit of detection (LOD)=60 ng/mL), linearity (0.2-20 µg/mL concentration range; y=23848(±361)X, n=15; r(2) =0.987) and precision (RSD<9%) by using an internal standard method. The PK results were discussed in terms of Area Under the Curve, Cmax and Tmax . Data reliability was demonstrated by comparison with a liquid chromatography-tandem mass spectrometry method (p>0.05). The data achieved demonstrated that the DESI-MS method is suitable for sensitive and fast profiling of a drug and its metabolites at the therapeutic concentration levels.

    Topics: Animals; Area Under Curve; Biotransformation; Chromatography, High Pressure Liquid; Esomeprazole; Limit of Detection; Liquid-Liquid Extraction; Male; Omeprazole; Proton Pump Inhibitors; Rats; Rats, Wistar; Reference Standards; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

2016
Determination of esomeprazole and its two main metabolites in human, rat and dog plasma by liquid chromatography with tandem mass spectrometry.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2007, Apr-01, Volume: 848, Issue:2

    A LC-MS/MS method was developed for quantitative determination of esomeprazole, and its two main metabolites 5-hydroxyesomeprazole and omeprazole sulphone in 25 microL human, rat or dog plasma. The analytes and their internal standards were extracted from plasma into methyl tert-butyl ether - dichloromethane (3:2, v/v). After evaporation and reconstitution of the organic extract the analytes were separated on a reversed-phase LC column and measured by atmospheric-pressure positive ionisation MS. The linearity range was 20-20,000 nmol/L for esomeprazole and omeprazole sulphone, and 20-4000 nmol/L for 5-hydroxyesomeprazole. The extraction recoveries ranged between 80 and 105%. The intra- and inter-day imprecision were less than 9.5% with accuracy between 97.7% and 100.1% for all analytes.

    Topics: Animals; Calibration; Chromatography, Liquid; Dogs; Esomeprazole; Humans; Molecular Structure; Omeprazole; Rats; Reproducibility of Results; Tandem Mass Spectrometry

2007