Lansoprazole sulfone
(Synonyms: 兰索拉唑磺酸盐) 目录号 : GC44033
A metabolite of lansoprazole
Cas No.:131926-99-3
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
Lansoprazole sulfone is a phase I metabolite of lansoprazole . Lansoprazole is a proton pump inhibitor that inactivates the hydrogen/potassium-stimulated ATPase pumps in parietal cells, thus inhibiting gastric acid secretion and increasing intragastric pH. Lansoprazole is metabolized by the cytochrome P450 (CYP) isoform CYP3A4 to form lansoprazole sulfone.
| Cas No. | 131926-99-3 | SDF | |
| 别名 | 兰索拉唑磺酸盐 | ||
| Canonical SMILES | CC1=C(CS(C2=NC(C=CC=C3)=C3N2)(=O)=O)N=CC=C1OCC(F)(F)F | ||
| 分子式 | C16H14F3N3O3S | 分子量 | 385.4 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml,Ethanol: 5 mg/ml | 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 | 2.5947 mL | 12.9735 mL | 25.9471 mL |
| 5 mM | 0.5189 mL | 2.5947 mL | 5.1894 mL |
| 10 mM | 0.2595 mL | 1.2974 mL | 2.5947 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。
Potential of lansoprazole as a novel probe for cytochrome P450 3A activity by measuring Lansoprazole sulfone in human liver microsomes
Biol Pharm Bull 2009 Aug;32(8):1422-6.PMID:19652384DOI:10.1248/bpb.32.1422.
Cytochrome P450 (CYP) 3A enzymes are responsible for the metabolism of many drugs. It is useful to know CYP3A activity in individual patients undergoing drug therapy so as to predict the efficacies or adverse events. Lansoprazole is metabolized to Lansoprazole sulfone (LS) by CYP3A, while to 5-hydroxylansoprasole by CYP2C19. The aim of this study was to evaluate whether lansoprazole can be used to assess CYP 3A activity in human liver. Lansoprazole sulfoxidation activity in 14 human liver microsomes was determined as the ratio of lansoprazole/LS, measuring these parameters by high-performance liquid chromatography. Testosterone 6beta-hydroxylation (T6beta-OH) activity, a known marker for CYP3A activity was also measured together with lansoprazole sulfoxidation activity. Lansoprazole sulfoxidation activity was also analyzed in microsomes preincubat-ed with anti-CYP2C19 antibody. Interindividual variation was observed in lansoprazole sulfoxidation activity and T6beta-OH activities of those microsomes, respectively. Lansoprazole sulfoxidation activity was significantly correlated with T6beta-OH activity and CYP3A protein level. Lansoprazole sulfoxidation activity in microsomes with anti-CYP2C19 antibody was closely correlated with T6beta-OH activity. In contrast, lansoprazole 5-hydroxylation activity was correlated with the CYP2C19 activity. These results suggest that metabolism of lansoprazole to LS by CYP3A occurs independently of metabolism by CYP2C19. LS can be used as a new marker of CYP3A activity.
Pharmacokinetic properties of lansoprazole (30-mg enteric-coated capsules) and its metabolites: A single-dose, open-label study in healthy Chinese male subjects
Curr Ther Res Clin Exp 2009 Jun;70(3):228-39.PMID:24683233DOI:10.1016/j.curtheres.2009.05.002.
Background: Lansoprazole, a benzimidazole derivative, is indicated for the treatment of various peptic diseases. It is metabolized mainly in the liver, and its primary active metabolites present in plasma are 5'-hydroxy lansoprazole and Lansoprazole sulfone. Few data are available on the pharmacokinetic properties of lansoprazole, 5'-hydroxy lansoprazole, and Lansoprazole sulfone, which can be used to measure cytochrome P450 (CYP) 2C19 activity. Objectives: The aims of this study were to investigate the clinical plasma pharmacokinetic properties of lansoprazole and its metabolites in healthy Chinese male volunteers, and to assess the influences of CYP2C19 on the pharmacokinetics of lansoprazole. Methods: Healthy adult Chinese male volunteers were enrolled in this single-dose, open-label study. All patients received a single oral enteric capsule containing 30 mg of lansoprazole after a 12-hour overnight fast. Serial blood samples were collected immediately before (0 hour) and at 20, 40, 60, 90, 120, and 150 minutes and 3, 4, 6, 8, 10, 12, 15, and 24 hours after study drug administration. The plasma concentrations of lansoprazole, 5'-hydroxy lansoprazole, and Lansoprazole sulfone were determined using a validated internal standard high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic properties (including Cmax, Tmax, elimination t½ [t½z], mean residence time [MRT], AUC0-24, AUC0-∞, apparent oral clearance [CLz/F], and apparent volume of distribution [Vz/F]) were determined using the noncompartmental method. Results: Twenty volunteers (mean [SD] age, 34.9 [2.9] years; weight, 64.6 [2.2] kg; height, 171.3 [3.3] cm) were enrolled in and completed the study. The mean (SD) pharmacokinetic properties of lansoprazole were as follows: Cmax, 1047 (344) ng/mL; Tmax, 2.0 (0.7) hours; t½z, 2.24 (1.43) hours; MRT, 3.62 (0.87) hours; AUC0-24, 3388 (1484) ng/mL/h; AUC0-∞, 3496 (1693) ng/mL/h; CLz/F, 9.96 (3.74) L/h; and Vz/F, 32.83 (11.74) L. The findings with 5'-hydroxy lansoprazole and Lansoprazole sulfone, respectively, were as follows: Cmax, 111.2 (41.8) and 66.6 (52.9) ng/mL; Tmax, 2.1 (0.8) and 1.9 (0.8) hours; t½z, 2.31 (1.18) and 2.52 (1.54) hours; and AUC0-24, 317.0 (81.2) and 231.9 (241.7) ng/mL/h. No adverse events were reported throughout the study. Conclusions: In these healthy Chinese male volunteers administered a single oral dose of lansoprazole 30 mg, absorption of lansoprazole was rapid (mean Cmax, 1047 ng/mL; Tmax, ~2.0 hours). Its 2 primary active metabolites, 5'-hydroxy lansoprazole and Lansoprazole sulfone, were identified in measurable quantities in plasma (Cmax, 111.2 and 66.6 ng/mL, respectively; and Tmax, 2.1 and 1.9 hours). The plasma t½z did not appear to reflect the duration of suppression of gastric acid secretion: the t½z values of lansoprazole and the 2 metabolites were ~2 to 2.5 hours, while the acid-inhibitory effect lasted >24 hours. Cmax, AUC, and t½z of lansoprazole, and especially Lansoprazole sulfone, varied. Differences in metabolism types and/or genotype of CYP2C19 should be taken into account when planning a lansoprazole dosing regimen.
Metabolic disposition of lansoprazole in relation to the S-mephenytoin 4'-hydroxylation phenotype status
Clin Pharmacol Ther 1997 May;61(5):574-82.PMID:9164419DOI:10.1016/S0009-9236(97)90137-5.
Objective: To assess the possible involvement of CYP2C19 in the metabolism of lansoprazole in vivo. Methods: Sixteen male Korean subjects, who had been phenotyped as extensive metabolizers and poor metabolizers of S-mephenytoin 4'-hydroxylation polymorphism (n = 8 each) with racemic mephenytoin with use of the 8-hour urine analysis of 4'-hydroxymephenytoin, took an oral dose of 30 mg lansoprazole, and blood samples were collected up to 48 hours after dosing. Lansoprazole and its metabolites were measured by high-performance liquid chromatography with ultraviolet detection. Results: The mean lansoprazole area under the concentration-time curve (AUC), elimination half-life (t1/2), and apparent oral clearance (CLoral) were significantly (p < 0.001) greater, longer, and lower, respectively, in the poor metabolizer than in the extensive metabolizer group. The mean values for the AUC of hydroxylansoprazole and AUC ratio of hydroxylansoprazole to lansoprazole were significantly (p < 0.01 to p < 0.001) less in the poor metabolizer than in the extensive metabolizer group, whereas those for the AUC of Lansoprazole sulfone and ratio of Lansoprazole sulfone to lansoprazole were greater (p < 0.001) in the former than in the latter group. In addition, the log10 4'-hydroxymephenytoin excreted in urine correlated significantly (p < 0.01) with the CLoral of lansoprazole. Conclusions: These results suggest that the hydroxylation of lansoprazole cosegregates with the genetically determined S-mephenytoin 4'-hydroxylation (CYP2C19) polymorphism in the Korean subjects.
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.