25-Desacetyl Rifampicin
(Synonyms: 25-乙酰-3-[(五)-[(4-甲基-1-哌嗪基)亚胺]甲基]利福霉素) 目录号 : GC49365
A major active metabolite of rifampicin
Cas No.:16783-99-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
25-Desacetyl rifampicin is a major active metabolite of the rifamycin antibiotic rifampicin .1 25-Desacetyl rifampicin is active against M. smegmatis (MIC99 = 2.66 µM).
1.Kigondu, E.M., Njoroge, M., Singh, K., et al.Synthesis and synergistic antimycobacterial screening of chlorpromazine and its metabolitesMed. Chem. Commun.5502-506(2014)
| Cas No. | 16783-99-6 | SDF | |
| 别名 | 25-乙酰-3-[(五)-[(4-甲基-1-哌嗪基)亚胺]甲基]利福霉素 | ||
| Canonical SMILES | OC1=C(C(C(O)=C2C)=C(O)C(NC(/C(C)=C\C=C\[C@@H]([C@@H]3O)C)=O)=C1/C=N/N4CCN(C)CC4)C5=C2O[C@@](C5=O)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]3C)O)C)O)C)OC)C | ||
| 分子式 | C41H56N4O11 | 分子量 | 780.9 |
| 溶解度 | DMSO: slightly soluble | 储存条件 | -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 | 1.2806 mL | 6.4029 mL | 12.8057 mL |
| 5 mM | 0.2561 mL | 1.2806 mL | 2.5611 mL |
| 10 mM | 0.1281 mL | 0.6403 mL | 1.2806 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。
Relationship between CES2 genetic variations and rifampicin metabolism
J Antimicrob Chemother 2013 Jun;68(6):1281-4.PMID:23471941DOI:10.1093/jac/dkt036.
Objectives: Rifampicin is known to be deacetylated in vivo, resulting in its metabolite 25-Desacetyl Rifampicin, but the enzyme metabolizing rifampicin and the association of this process with any genetic variation have not yet been elucidated. In this study, genetic variations of a surrogate enzyme, carboxylesterase 2 (CES2), and their association with the metabolism of this drug, were investigated. Methods: Plasma concentrations of rifampicin and 25-Desacetyl Rifampicin were measured in 35 patients with tuberculosis receiving a first-line antituberculosis treatment. Direct PCR-based sequencing of the CES2 gene, covering all 12 exons, the 5'-untranslated region (UTR), the 3'-UTR and intronic and promoter regions, was performed. A dual luciferase reporter assay was carried out to assess whether variations in the promoter region affected the transcription of this gene. Results: Ten variations were detected, of which two were in the candidate promoter region, five in introns and three in the 3'-UTR. One of the variations in the 3'-UTR was a novel variation. Genotypes at three closely linked variations (c.-2263A > G, c.269-965A > G and c.1612 + 136G > A) and c.1872*302_304delGAA were associated with significantly different plasma rifampicin concentrations. The mean plasma rifampicin concentration significantly increased with the number of risk alleles at the three closely linked variations, while the plasma concentration decreased along with an increase in the number of risk alleles at c.1872*302_304delGAA. When HepG2 cells were transfected with a luciferase reporter construct bearing the c.-2263G allele, luciferase activities were consistently decreased (by 5%-10%) compared with those harbouring the c.-2263A sequence. Conclusions: Variations in CES2, especially c.-2263A > G in the promoter region, may alter rifampicin metabolism by affecting expression of the gene.
Population Pharmacokinetic Analysis of Rifampicin in Plasma, Cerebrospinal Fluid, and Brain Extracellular Fluid in South African Children with Tuberculous Meningitis
Antimicrob Agents Chemother 2023 Mar 16;67(3):e0147422.PMID:PMC10019224DOI:10.1128/aac.01474-22.
Limited knowledge is available on the pharmacokinetics of rifampicin in children with tuberculous meningitis (TBM) and its penetration into brain tissue, which is the site of infection. In this analysis, we characterize the distribution of rifampicin in cerebrospinal fluid (CSF), lumbar (LCSF) and ventricular (VCSF), and brain extracellular fluid (ECF). Children with TBM were included in this pharmacokinetic analysis. Sparse plasma, LCSF, and VCSF samples were collected opportunistically, as clinically indicated. Brain ECF was sampled using microdialysis (MD). Rifampicin was quantified with liquid chromatography with tandem mass spectrometry in all samples, and 25-Desacetyl Rifampicin in the plasma samples. The data were interpreted with nonlinear mixed-effects modeling, with the CSF and brain ECF modeled as "effect compartments." Data were available from 61 children, with median (min-max) age of 2 (0.3 to 10) years and weight of 11.0 (4.8 to 49.0) kg. A one-compartment model for parent and metabolite with first-order absorption and elimination via saturable hepatic clearance described the data well. Allometric scaling, maturation, and auto-induction of clearance were included. The pseudopartition coefficient between plasma and LCSF/VCSF was ~5%, while the value for ECF was only ~0.5%, possibly reflecting low recovery of rifampicin using MD. The equilibration half-life between plasma and LCSF/VCSF was ~4 h and between plasma and ECF ~2 h. Our study confirms previous reports showing that rifampicin concentrations in the LCSF are lower than in plasma and provides novel knowledge about rifampicin in the VCSF and the brain tissue. Despite MD being semiquantitative because the relative recovery cannot be quantified, our study presents a proof-of-concept that rifampicin reaches the brain tissue and that MD is an attractive technique to study site-of-disease pharmacokinetics in TBM.
A bioequivalence comparison of two formulations of rifampicin (300- vs 150-mg capsules): An open-label, randomized, two-treatment, two-way crossover study in healthy volunteers
Clin Ther 2010 Sep;32(10):1822-31.PMID:21194606DOI:10.1016/j.clinthera.2010.09.006.
Background: Rifampicin is a semisynthetic antibiotic derivative of rifamycin used worldwide for the treatment of various forms of tuberculosis. Objective: The objective of this study was to compare, under fasting conditions in healthy volunteers, the rate and extent of absorption of a generic rifampicin capsule in oral dosage form versus the proprietary equivalent formulation for the purpose of registration approval of the test formulation. Methods: This was an open-label, randomized, 2-treatment, 2-way crossover study with an 8-week washout period between the 2 study arms. Healthy volunteers received a 300-mg capsule of the test formulation (Idaman Pharma Manufacturing Sdn. Bhd.) or two 150-mg capsules of the reference formulation. Blood samples were collected predose and at 45 minutes and 1.25, 1.5, 2, 2.25, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours postdose. Plasma concentrations of rifampicin and its metabolite, 25-Desacetyl Rifampicin, were analyzed using a validated HPLC method. The formulations were considered bioequivalent if the 90% CIs for C(max) and AUC were within the predetermined bioequivalence range (80%-125%, according to the guidelines of the US Food and Drug Administration, or 75%-133% for Cmax only, as set by the European Commission-European Medicines Agency and the National Pharmaceutical Control Bureau of Malaysia). Tolerability was assessed by verbally questioning subjects regarding their well-being and any feelings of discomfort. All events reported by the subjects (serious or mild) were recorded on adverse-event forms. Results: Fourteen healthy subjects (10 males, 4 females) with a mean age of 22.6 years (range, 20-28 years) and a mean body mass index of 22.2 kg/m² (range, 18.3-29.9 kg/m²) were enrolled in the study; all 14 completed the trial as outlined in the protocol. The mean values for C(max), T(max) , AUC₀₋₂₄, and AUC₀₋(∞)) with the test formulation of rifampicin were 7.20 μg/mL, 1.32 hours, 37.12 μg/mL · h, and 39.69 μg/mL · h, respectively; for the reference formulation, the values were 7.65 μg/mL, 1.71 hours, 38.92 μg/mL · h, and 42.24 μg/ mL · h. For 25-Desacetyl Rifampicin, the mean values for C(max), T(max), AUC₀₋₂₄, and AUC₀₋(∞)) with the test formulation were 0.63 μg/mL, 3.45 hours, 4.92 μg/mL · h, and 6.27 μg/mL · h; for the reference formulation, the values were 0.7 μg/mL, 3.27 hours, 5.23 μg/mL · h, and 6.84 μg/mL · h. For rifampicin, the 90% CIs for the test formulation/reference formulation ratio for the logarithmic transformations of both C(max) and AUC₀₋(∞)) were within the bioequivalence limit of 80% to 125% (80.9109.7 and 80.7-103.2, respectively). For 25-Desacetyl Rifampicin, the 90% CI for the test formulation/reference formulation ratio for the logarithmic transformations of AUC₀₋₂₄ (80.0-104.7) was within the bioequivalence limit of 80% to 125%. However, the 90% CI for C(max) (78.4-102.2) was outside this limit but still within the acceptance limit for Cmax when adhering to the bioequivalence range of 75% to 133%. No adverse events were reported during the study. Conclusions: This study found that the 300-mg test capsule and the 150-mg reference capsules of rifampicin met the regulatory criteria for assuming bioequivalence in these fasting healthy volunteers. Both formulations appeared to be well tolerated in the population studied.
Evaluation of the recently reported USP gradient HPLC method for analysis of anti-tuberculosis drugs for its ability to resolve degradation products of rifampicin
J Pharm Biomed Anal 2003 Mar 10;31(3):607-12.PMID:12615251DOI:10.1016/s0731-7085(02)00715-x.
The recently notified USP gradient HPLC method for quantitative determination of rifampicin, isoniazid and pyrazinamide in fixed dose combination (FDC) formulations was evaluated to determine its ability to resolve major degradation products of rifampicin, viz. 3-formylrifamycin SV, rifampicin N-oxide, 25-Desacetyl Rifampicin, rifampicin quinone, and the newly reported isonicotinyl hydrazone, an interaction product of 3-formylrifamycin and isoniazid. The first observation was that the requirements of theoretical plates listed in the given method were met for rifampicin, but not for isoniazid and pyrazinamide, even on columns of different makes. The resolving power of the method was also dependent upon make of the column. On two of the three columns of the three tested, it was able to resolve most degradation products, except rifampicin N-oxide and 25-desacetylrifampicin, which were overlapping. The method was modified and an overall satisfactory resolution for all components was obtained by changing the buffer: organic modifier ratio of solution B in the gradient from 45:55 to 55:45 and decreasing the flow rate from 1.5 to 1.0 ml/min, keeping all other conditions constant.