5-hydroxy Omeprazole
(Synonyms: 5-羟基奥美拉唑) 目录号 : GC41312A major metabolite of omeprazole
Cas No.:92340-57-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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5-hydroxy Omeprazole is a major metabolite of omeprazole , an inhibitor of the gastric H+/K+-ATPase pump.[1] 5-hydroxy Omeprazole is produced from omeprazole by the action of cytochrome P450 (CYP) isoform 2C19, a monooxygenase. [2][3] CYP2C19 polymorphisms significantly influence the metabolism of omeprazole, and individuals may be classified as homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers.[1]
Reference:
[1]. Shi, S., and Klotz, U. Proton pump inhibitors: An update of their clinical use and pharmacokinetics. Eur. J. Clin. Pharmacol. 64(10), 935-951 (2008).
[2]. Abelö, A., Andersson, T.B., Antonsson, M., et al. Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab. Dispos. 28(8), 966-972 (2000).
[3]. Karam, W.G., Goldstein, J.A., Lasker, J.M., et al. Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes. Drug Metab. Dispos. 24, 1081-1087 (1996).
| Cas No. | 92340-57-3 | SDF | |
| 别名 | 5-羟基奥美拉唑 | ||
| 化学名 | 4-methoxy-6-[[(6-methoxy-1H-benzimidazol-2-yl)sulfinyl]methyl]-5-methyl-3-pyridinemethanol | ||
| Canonical SMILES | COC1=CC=C2C(N=C(S(CC3=C(C)C(OC)=C(CO)C=N3)=O)N2[H])=C1 | ||
| 分子式 | C17H19N3O4S | 分子量 | 361.4 |
| 溶解度 | 10mg/mL in DMSO, 20mg/mL in DMF, 2mg/mL in Ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.767 mL | 13.8351 mL | 27.6702 mL |
| 5 mM | 0.5534 mL | 2.767 mL | 5.534 mL |
| 10 mM | 0.2767 mL | 1.3835 mL | 2.767 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pharmacokinetics of omeprazole and its metabolites in three phases of menstrual cycle
Eur J Drug Metab Pharmacokinet 2015 Mar;40(1):13-22.PMID:24390778DOI:10.1007/s13318-013-0167-4.
Omeprazole (OMP) is effective in the treatment of gastric hyperacidity and is metabolized by CYP2C19 and CYP3A4. These enzymes are modulated by estrogen and progesterone which regulate the menstrual cycle. The variations in the pharmacokinetics (PK) of many drugs like amphetamine, benzodiazepines and caffeine have been reported during menstrual cycle. In present study, the PK of the omeprazole and its metabolites was investigated during various phases of the menstrual cycle. A single oral dose, open-label, non-controlled, pharmacokinetic study of omeprazole was conducted in healthy young/premenopausal females (n = 16). The PK of omeprazole, 5-hydroxy-omeprazole and omeprazole sulphone was evaluated in three phases of menstrual cycle. The blood samples were analyzed using reversed-phase HPLC coupled with UV detector and the PK data were evaluated. The activities of CYP2C19 and CYP3A4 were determined as AUC(OH-OMP)/AUC(OMP) and AUC(OMP-SUL)/AUC(OMP), respectively. Omeprazole showed significantly (p < 0.05) higher [Formula: see text] and CL/F in follicular and menstrual phases, respectively. The [Formula: see text] of 5-hydroxy Omeprazole was also significantly (p < 0.05) higher in follicular phase. The metabolic ratios (MR) of 5-hydroxy Omeprazole and omeprazole sulphone were lower in follicular phase compared with the luteal phase. The present study suggests that high estrogen levels of follicular phase may result in increased absorption of omeprazole. The lower MR for 5-hydroxy Omeprazole and omeprazole sulphone in follicular phase as compared to luteal phase suggests that metabolism of omeprazole is low in follicular phase as compared to luteal phase, which is progesterone-dominant phase. However, the clinical significance for these findings needs to be determined.
Comparative pharmacokinetics of Omeprazole and its metabolites in poor and extensive metabolizer Pakistani healthy volunteers and a review of different studies
Pak J Pharm Sci 2018 Jul;31(4):1363-1374.PMID:30033421doi
This study was designed to evaluate a comparative single dose (40mg) pharmacokinetics (PK) of Omeprazole (OMP) and its two metabolites, 5-hydroxy Omeprazole (5-OH-OMP) and Omeprazole sulphone (OMP-S) in poor (PM) and extensive (EM) metabolizer Pakistani healthy adult volunteers. The frequency of CYP2C19 and CYP3A4 varies widely in different populations. The present study was conducted to evaluate the PK of OMP and its two metabolites in Pakistani population and to review different studies conducted after administration of single dose of OMP. Twenty two subjects were enrolled in this study and divided into two groups. The CYP2C19 phenotyping was evaluated by the metabolic ratio of OMP to 5-OH-OMP. It was a single dose, open label study and the blood samples from subjects were collected at different time intervals until 24 hours. The PK parameters were calculated using the PK-summit software. The metabolic ratio of area under the plasma concentration-time curve AUCOMP/5-OH-OMP was 1.86 ± 0.572 and13.84 ± 2.504 for EM and PM, respectively; maximum plasma concentration (Cmax) of OMP was increased by two folds for PM while the AUC∞ was increased by 3 folds; the Cmax and AUC∞ of 5-OH-OMP decreased for PM by 2 folds while there was 3 fold increase observed in the Cmax and AUC∞ of OMP-S. The PK of OMP and its metabolites in different populations were also discussed, and issues regarding CYP2C19 and CYP3A4 genotyping were also extensively reviewed. In EM of CYP2C19 the concentration of 5-OH-OMP is higher while that of OMP-S is lower. This study as well as reported studies reveals that in PM of CYP2C19 more drugs are available for CYP3A4 to be metabolized. A correlation between CYP2C19 EM and PM activity with CYP3A4 needs to be established.
Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers
Br J Clin Pharmacol 2008 May;65(5):767-74.PMID:18294333DOI:10.1111/j.1365-2125.2008.03104.x.
What is already known about this subject: The only existing study of CYP2C19*17-associated alterations in drug pharmacokinetics was retrospective and compared probe drug metabolic ratios. The CYP2C19*17 allele had been associated with a two- and fourfold decrease in omeprazole and S/R-mephenytoin metabolic ratios. What this study adds: This study characterized the single-dose pharmacokinetics of omeprazole, along with the 5-hydroxy and sulphone metabolites, in CYP2C19*17/*17 and CYP2C19*1/*1 subjects. The observed differences in omeprazole AUC(infinity) suggest that the CYP2C19*17 allele is an important explanatory factor behind individual cases of therapeutic failure. AIMS To investigate the influence of the CYP2C19*17 allele on the pharmacokinetics of omeprazole, a commonly used CYP2C19 probe drug, in healthy volunteers. Methods: In a single-dose pharmacokinetic study, 17 healthy White volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1 received an oral dose of 40 mg of omeprazole. Plasma was sampled for up to 10 h postdose, followed by quantification of omeprazole, 5-hydroxy Omeprazole and omeprazole sulphone by high-performance liquid chromatography. Results: The mean omeprazole AUC(infinity) of 1973 h nmol l(-1) in CYP2C19*17/*17 subjects was 2.1-fold lower [95% confidence interval (CI) 1.1, 3.3] than in CYP2C19*1/*1 subjects (4151 h nmol l(-1), P = 0.04). A similar trend was observed for the sulphone metabolite with the CYP2C19*17/*17 group having a mean AUC(infinity) of 1083 h nmol l(-1), 3.1-fold lower (95% CI 1.2, 5.5) than the CYP2C19*1/*1 group (3343 h nmol l(-1), P = 0.03). A pronounced correlation (r(2) = 0.95, P < 0.0001) was seen in the intraindividual omeprazole AUC(infinity) and omeprazole sulphone AUC(infinity) values. Conclusions: The pharmacokinetics of omeprazole and omeprazole sulphone differ significantly between homozygous CYP2C19*17 and CYP2C19*1 subjects. For clinically important drugs that are metabolized predominantly by CYP2C19, the CYP2C19*17 allele might be associated with subtherapeutic drug exposure.
Simultaneous determination of omeprazole and their main metabolites in human urine samples by capillary electrophoresis using electrospray ionization-mass spectrometry detection
J Pharm Biomed Anal 2014 Apr;92:211-9.PMID:24530982DOI:10.1016/j.jpba.2013.12.020.
We report a novel method for the simultaneous determination of omeprazole and their main metabolites (omeprazole sulphide, omeprazole sulphone and 5-hydroxy Omeprazole) in human urine samples. For this purpose, two new capillary electrophoresis (CE) methods were developed for the simultaneous determination of target compounds, using initially diode-array for optical detection and electrospray ionization-mass spectrometry (ESI-MS) for metabolites identification and identity confirmation. A new metabolite (5-hydroxysulphide omeprazole) was identified by electrospray ionization multi-stage mass spectrometry (ESI-MS2) fragment which was then used to support the proposed chemical structure. Pharmacokinetic results using CE method were compared with those obtained when a HPLC method was used. Equivalent pharmacokinetics profiles resulted when any analytical methods were carried out.
Prediction of cytochromes P450 3A and 2C19 modulation by both inflammation and drug interactions using physiologically based pharmacokinetics
CPT Pharmacometrics Syst Pharmacol 2022 Jan;11(1):30-43.PMID:34791831DOI:10.1002/psp4.12730.
Xenobiotics can interact with cytochromes P450 (CYPs), resulting in drug-drug interactions, but CYPs can also contribute to drug-disease interactions, especially in the case of inflammation, which downregulates CYP activities through pretranscriptional and posttranscriptional mechanisms. Interleukin-6 (IL-6), a key proinflammatory cytokine, is mainly responsible for this effect. The aim of our study was to develop a physiologically based pharmacokinetic (PBPK) model to foresee the impact of elevated IL-6 levels in combination with drug interactions with esomeprazole on CYP3A and CYP2C19. Data from a cohort of elective hip surgery patients whose CYP3A and CYP2C19 activities were measured before and after surgery were used to validate the accurate prediction of the developed models. Successive steps were to fit models for IL-6, esomeprazole, and omeprazole and its metabolite from the literature and to validate them. The models for midazolam and its metabolite were obtained from the literature. When appropriate, a correction factor was applied to convert drug concentrations from whole blood to plasma. Mean ratios between simulated and observed areas under the curve for omeprazole/5-hydroxy Omeprazole, esomeprazole, and IL-6 were 1.53, 1.06, and 0.69, respectively, indicating an accurate prediction of the developed models. The impact of IL-6 and esomeprazole on the exposure to CYP3A and CYP2C19 probe substrates and respective metabolites were correctly predicted. Indeed, the ratio between predicted and observed mean concentrations were <2 for all observations (ranging from 0.51 to 1.7). The impact of IL-6 and esomeprazole on CYP3A and CYP2C19 activities after a hip surgery were correctly predicted with the developed PBPK models.