5-Hydroxylansoprazole
(Synonyms: 5-羟基兰索拉唑,AG1908) 目录号 : GC60530
5-Hydroxylansoprazole(AG1908)是血浆中Lansoprazole的活性代谢产物。Lansoprazole由CYP2C19代谢形成5-Hydroxylansoprazole。Lansoprazole是一种胃质子泵(proton-pump)抑制剂，可有效研究各种消化系统疾病。
Cas No.:131926-98-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
5-Hydroxylansoprazole (AG1908) is an active metabolite of Lansoprazole in plasma. Lansoprazole is metabolized by CYP2C19 forming 5-Hydroxylansoprazole. Lansoprazole is a gastric proton-pump inhibitor and is effective in the treatment of various peptic diseases[1][2].
[1]. Xu HR, et al. The effect of CYP2C19 activity on pharmacokinetics of lansoprazole and its active metabolites in healthy subjects. Pharm Biol. 2010 Aug;48(8):947-52. doi: 10.3109/13880200903300220. [2]. KatarÍna KostolanskÁ, et al. Determination of lansoprazole, 5-hydroxylansoprazole, and lansoprazole sulfone in human plasma for CYP2C19 and CYP3A4 phenotyping. Chemical Papers. volume 73, pages2955-2963(2019).
| Cas No. | 131926-98-2 | SDF | |
| 别名 | 5-羟基兰索拉唑,AG1908 | ||
| Canonical SMILES | OC1=CC=C2N=C(NC2=C1)S(CC3=NC=CC(OCC(F)(F)F)=C3C)=O | ||
| 分子式 | C16H14F3N3O3S | 分子量 | 385.36 |
| 溶解度 | 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 | 2.595 mL | 12.9749 mL | 25.9498 mL |
| 5 mM | 0.519 mL | 2.595 mL | 5.19 mL |
| 10 mM | 0.2595 mL | 1.2975 mL | 2.595 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。
Pharmacokinetic differences between the enantiomers of lansoprazole and its metabolite, 5-Hydroxylansoprazole, in relation to CYP2C19 genotypes
Eur J Clin Pharmacol 2004 Nov;60(9):623-8.PMID:15448955DOI:10.1007/s00228-004-0809-1.
Objective: The purpose of this study was to elucidate the pharmacokinetics of each enantiomer of lansoprazole and 5-Hydroxylansoprazole in three different CYP2C19 genotype groups of Japanese subjects. Methods: Healthy subjects ( n=18), of whom 6 were homozygous extensive metabolizers (homEMs), 6 were heterozygous extensive metabolizers (hetEMs) and 6 were poor metabolizers (PMs), participated in the study. After a single oral dose of 60 mg of racemic lansoprazole, the plasma concentrations of the lansoprazole enantiomers, 5-Hydroxylansoprazole enantiomers and lansoprazole sulfone were measured for 24 h post-dose. Results: The plasma concentrations of ( R)-lansoprazole were remarkably higher in all three CYP2C19 genotype groups than those of the corresponding ( S)-enantiomer. The mean maximum plasma concentration ( C(max)) of ( S)-lansoprazole differed significantly among the three groups, whereas there was no difference for the ( R)-enantiomer. The relative area under the plasma concentration (AUC) ratios of ( R)- and ( S)-lansoprazole in the homEMs, hetEMs, and PMs were 1:1.5:4.0 and 1:1.8:7.4, respectively. Yet, the relative AUC ratios of 5-Hydroxylansoprazole to lansoprazole for the ( R)- and ( S)-enantiomers in the homEMs, hetEMs, and PMs were almost the same (1:0.73:0.12 and 1:0.77:0.13, respectively). However, the AUC ratios of the ( S)-enantiomer were 13-fold greater for the three CYP2C19 genotypes than those of the corresponding ( R)-enantiomer. Conclusions: The magnitude of the contribution of CYP2C19 to the 5-hydroxylation of ( S)-lansoprazole was greater than that of the ( R)-enantiomer. The R/S ratios for the AUC of lansoprazole for the homEMs, hetEMs and PMs were 12.7, 8.5 and 5.8, respectively, suggesting a significant effect of CYP2C19 polymorphisms on the stereoselective disposition of lansoprazole.
Effect of clarithromycin and other macrolides on the sulfoxidation and 5-hydroxylation of lansoprazole in dogs
Biol Pharm Bull 1999 May;22(5):504-9.PMID:10375172DOI:10.1248/bpb.22.504.
The purpose of this study was to evaluate a possible interaction between lansoprazole and clarithromycin as well as other macrolides in dogs. Lansoprazole (30 mg) was orally administered to male beagle dogs, with or without oral pretreatment with 200-mg clarithromycin twice a day for 5 d. The experiments had a randomized cross-over design with a two-week washout period between dosing regimens. Clarithromycin pretreatment for 5 d resulted in a significant increase in the area under the serum lansoprazole concentration-time curve (AUC), whereas the area for a lansoprazole metabolite, lansoprazole sulfone, was significantly reduced, as was the maximum serum concentration (Cmax) of lansoprazole sulfone. When the effects of clarithromycin on the metabolism of lansoprazole were studied using dog liver microsomes, it was found that clarithromycin significantly inhibited the formation of lansoprazole sulfone but not another metabolite, 5-Hydroxylansoprazole. These results suggest that co-medication of lansoprazole with clarithromycin may produce a synergistic effect caused by the increased serum levels of lansoprazole of benefit in Helicobacter pylori eradication.
Identification of the human P450 enzymes involved in lansoprazole metabolism
J Pharmacol Exp Ther 1996 May;277(2):805-16.PMID:8627562doi
The aim of this study was to identify which human P450 enzymes are involved in the metabolism of lansoprazole. In the presence of NADPH and oxygen, human liver microsomes converted lansoprazole to lansoprazole sulfide, lansoprazole sulfone and 5-Hydroxylansoprazole. Formation of lansoprazole sulfide occurred nonenzymatically. The formation of lansoprazole sulfone appeared to be catalyzed by a single, low-affinity enzyme (apparent Km approximately 100 microM). In contrast, lansoprazole 5-hydroxylation appeared to be catalyzed by two kinetically distinct enzymes (apparent Km approximately 100 microM and approximately 15 microM). When human liver microsomes (n = 16) were incubated with 100 microM lansoprazole, both the 5-hydroxylation and sulfoxidation of lansoprazole appeared to be catalyzed by CYP3A4/5 (based on correlation analyses). Antibodies against rat CYP3A enzymes inhibited the rate of both 5-hydroxylation (approximately 55%) and sulfoxidation (approximately 70%) and cDNA-expressed CYP3A4 catalyzed both the 5-hydroxylation and sulfoxidation of lansoprazole (apparent Km approximately 100 microM). However, at the pharmacologically relevant substrate concentration of 1 microM, lansoprazole sulfoxidation was still highly correlated with CYP3A4/5 activity (r2 = .905), but lansoprazole 5-hydroxylation appeared to be catalyzed by CYP2C19 (r2 = .875) rather than CYP3A4/5 (r2 = .113). Antibodies and chemical inhibitors of CYP2C enzymes preferentially inhibited the 5-hydroxylation of lansoprazole, whereas lansoprazole sulfoxidation was preferentially inhibited by antibodies and chemical inhibitors of CYP3A4/5. The cDNA expressed enzymes CYP2C8, CYP2C9 and CYP2C19 catalyzed varying rates of lansoprazole 5-hydroxylation at a substrate concentration of 50 microM, but only CYPC19 catalyzed this reaction at 1 microM. These results suggest that at pharmacologically relevant concentrations, the 5-hydroxylation of lansoprazole is primarily catalyzed by CYP2C19, whereas the sulfoxidation of lansoprazole is primarily catalyzed by CYP3A4/5. It is possible that individuals lacking CYP2C19 will be poor metabolizers of lansoprazole.
The effect of CYP2C19 activity on pharmacokinetics of lansoprazole and its active metabolites in healthy subjects
Pharm Biol 2010 Aug;48(8):947-52.PMID:20673183DOI:10.3109/13880200903300220.
Context: Lansoprazole is a gastric proton-pump inhibitor and has been demonstrated to be effective in the treatment of various peptic diseases. The effects of CYP2C19 activity on the pharmacokinetics of lansoprazole and its active metabolites in Chinese subjects have not previously been evaluated. Objective: The study aimed to evaluate the effects of CYP2C19 activity in healthy Chinese volunteers. Materials and methods: Twenty-two healthy volunteers were recruited for an open trial and received a single dose of 30 mg lansoprazole. Using a validated LC-MS/MS method, we measured the plasma concentrations of lansoprazole, 5-Hydroxylansoprazole, and lansoprazole sulfone. The genotype of CYP2C19 was identified by polymerase chain reaction (PCR) analysis of single nucleotide polymorphisms (SNPs). Subjects were genotypically classified into the following three groups on the basis of PCR-SNP analysis for CYP2C19: homozygous EM (hmEM) group, heterozygous EM (htEM) group, and PM group. To test differences in pharmacokinetic parameters among the three groups, analysis of variance (ANOVA) after log-transformation of data was used. Results and conclusion: Our results indicated that there were significant differences (p < 0.001) between the hmEM and PM groups, between the htEM and PM groups, and between the hmEM and htEM groups in C(max), AUC(0-t), and AUC(0-inf) of lansoprazole and lansoprazole sulfone. There were also significant differences (p < 0.001) between the hmEM and PM groups, and between the htEM and PM groups in C(max) of 5-Hydroxylansoprazole.
Determination of lansoprazole and two of its metabolites by liquid-liquid extraction and automated column-switching high-performance liquid chromatography: application to measuring CYP2C19 activity
J Chromatogr B Analyt Technol Biomed Life Sci 2005 Feb 25;816(1-2):309-14.PMID:15664363DOI:10.1016/j.jchromb.2004.11.052.
A simple and sensitive column-switching high-performance liquid chromatographic (HPLC) method for the simultaneous determination of lansoprazole, a proton pump inhibitor and its major metabolites: 5-Hydroxylansoprazole and lansoprazole sulfone in human plasma. The test compounds were extracted from 1 mL of plasma using diethyl ether-dichloromethane (7:3, v/v) mixture and the extract was injected into a column I (TSK-PW precolumn, 10 microm, 3.5 mm x 4.6 mm i.d.) for clean-up and column I (C(18) STR ODS-II analytical column, 5 microm, 150 mm x 4.6 mm i.d.) for separation. The peak was detected by a ultraviolet detector set at a wavelength of 285 nm, and the total time for a chromatographic separation was approximately 25 min. The method was validated for the concentration range from 3 to 5000 ng/mL. Mean recoveries were 74.0% for lansoprazole, 68.3% for 5-Hydroxylansoprazole, and 79.4% for lansoprazole sulfone. Intra- and inter-day relative standard derivatives were less than 6.1 and 5.1% for lansoprazole, 5.8 and 5.8% for 5-Hydroxylansoprazole, 4.4 and 5.9% for lansoprazole sulfone, respectively, at the different concentration ranges. This method is suitable for use in therapeutic drug monitoring and pharmacokinetic studies, and provides use tool for measuring CYP2C19 activity.