Erythromycylamine
(Synonyms: (9S)-红霉胺) 目录号 : GC45449
A macrolide antibiotic
Cas No.:26116-56-3
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
Erythromycylamine is a macrolide antibiotic and an active metabolite of dirithromycin .1 It is active against a variety of bacteria, including strains of S. pyogenes, S. pneumoniae, L. monocytogenes, and B. pertussis (MICs = 0.06-0.12, 0.06-0.12, 1-2, and 0.015-0.25 μg/ml, respectively). It is also active against 28 clinical isolates of M. avium complex (MAC) isolated from patients with AIDS (MICs = 4-16 μg/ml).2 Erythromycylamine inhibits polylysine and polyproline synthesis in a cell-free assay.3
References
1. Hardy, D.J., Hensey, D.M., Beyer, J.M., et al. Comparative in vitro activities of new 14-, 15-, and 16-membered macrolides. Antimicrob. Agents Chemother. 32(11), 1710-1719 (1988).
2. Naik, S., and Ruck, R. In vitro activities of several new macrolide antibiotics against Mycobacterium avium complex. Antimicrob. Agents Chemother. 33(9), 1614-1616 (1989).
3. Matija•evi•, P., Franji•, N., •oki•, S., et al. Erythromycin series. X. Inhibitory activity of several new erythromycin derivatives in cell-free amino acid polymerization systems. Croat. Chem. Acta 53(3), 519-524 (1980).
| Cas No. | 26116-56-3 | SDF | |
| 别名 | (9S)-红霉胺 | ||
| Canonical SMILES | C[C@H]1[C@H](O)[C@@](OC)(C)C[C@@](O[C@H]([C@H]2C)[C@H](C)[C@@H](O[C@@]3([H])[C@H](O)[C@@H](N(C)C)C[C@@H](C)O3)[C@](C)(O)C[C@@H](C)[C@H](N)[C@H](C)[C@@H](O)[C@](C)(O)[C@@H](CC)OC2=O)([H])O1 | ||
| 分子式 | C37H70N2O12 | 分子量 | 735 |
| 溶解度 | DMF: 15 mg/ml,DMSO: 15 mg/ml,Ethanol: 30 mg/ml,Ethanol:PBS (pH 7.2) (1:1): 0.5 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。 |
||
| 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 | 1.3605 mL | 6.8027 mL | 13.6054 mL |
| 5 mM | 0.2721 mL | 1.3605 mL | 2.7211 mL |
| 10 mM | 0.1361 mL | 0.6803 mL | 1.3605 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 dirithromycin
J Antimicrob Chemother 1993 Mar;31 Suppl C:65-75.PMID:8478313DOI:10.1093/jac/31.suppl_c.65.
Dirithromycin is a new member of the macrolide class of antibiotics and has been developed for oral administration. Dirithromycin is a 14-membered lactone ring macrolide and is the C9-oxazine derivative of Erythromycylamine. The human pharmacokinetics and clinical pharmacology of dirithromycin have been studied. Dirithromycin has unique pharmacokinetics which distinguish it from erythromycin. In man, following an oral 500 mg dose of dirithromycin, a mean peak plasma concentration (Cmax) of 0.48 mg/L (range 0.1-1.97) was observed at 4 h. The mean area under the plasma concentration versus time curve (AUC0-24h) measured 3.37 mg.h/L (range 0.39-17.16). No plasma accumulation was observed with multiple-dose administration. Dirithromycin may be taken without regard to meals, although food and H2-receptor antagonists may increase the systemic bioavailability in some patients. Based upon drug interaction studies performed with antipyrine and theophylline, dirithromycin has shown less potential to interact with other drugs metabolized by the cytochrome P450 system that does erythromycin. Plasma concentrations and AUCs were low due to rapid movement of the drug from the vascular space to the extravascular compartment, as reflected by tissue concentrations, which exceeded plasma concentrations 4 h after dosing. Dirithromycin achieves relatively high tissue concentrations (approximately 0.8-5.0 mg/kg) 4-24 h after dosing. The extensive tissue penetration is reflected in a large mean apparent volume of distribution of 800 L (range 504-1041). Dirithromycin is rapidly converted by non-enzymatic hydrolysis during absorption to Erythromycylamine, which is microbiologically active. In a 14C-radiolabelled study, 60-90% of the administered dose was hydrolysed to Erythromycylamine within 35 min of infusion. After 1.5 h, conversion to Erythromycylamine in serum was virtually complete. Plasma protein binding was determined to be 15-30% by ultracentrifugation. Dirithromycin is characterized by a plasma elimination half-life of 44 h (range 16-65 h) that permits once-daily administration. Total body clearance was 226-1040 mL/min in the 14C-radiolabelled study. The primary route of elimination of dirithromycin/Erythromycylamine was faecal/hepatic. Following intravenous administration, approximately 17-25% of the radioactivity appeared in the urine and 62-81% appeared in the stool, indicating predominantly hepatic excretion. With oral administration 1.2-2.9% of the radioactivity appeared in the urine and 81-97% in the stool. The major part of urinary excretion occurs within the first 48 h post-administration; however, urinary excretion of radioactivity lasted longer than 240 h. The absolute bioavailability calculated from dose-corrected urinary excretion data was 10% (6-14%).
Quantitative determination of Erythromycylamine in human plasma by liquid chromatography-mass spectrometry and its application in a bioequivalence study of dirithromycin
J Chromatogr B Analyt Technol Biomed Life Sci 2008 Mar 15;864(1-2):1-8.PMID:18296129DOI:10.1016/j.jchromb.2007.12.021.
A sensitive, rapid liquid chromatographic-electrospray ionization mass spectrometric method for determination of Erythromycylamine in human plasma was developed and validated. Erythromycylamine in plasma (0.2 mL) was extracted with ethyl acetate, the organic phase was transferred to another clear 1.5 mL Eppendorf tube and evaporated to dryness under gentle nitrogen stream at 45 degrees C, and the residue was dissolved in 100 microL of mobile phase. The samples were separated using a Thermo Hypersil HyPURITY C18 reversed-phase column (150 mm x 2.1 mm I.D., 5 microm). A mobile phase containing 10 mM of ammonium acetate (pH = 6.4)-acetonitrile-methanol (50:10:40, v/v/v) was used isocratically eluting at a flow rate of 0.2 mL/min. Erythromycylamine and its internal standard (IS), midecamycin, were measured by electrospray ion source in positive selective ion monitoring mode. The method demonstrated that good linearity ranged from 4.5 to 720 ng/mL with r = 0.9997. The limit of quantification for Erythromycylamine in plasma was 4.5 ng/mL with good accuracy and precision. The mean extraction recovery of the method was higher than 75.1% and 72.7% for Erythromycylamine and IS, respectively. The intra-day and inter-day precision ranged from 5.2% to 6.4% and 5.6-9.3% (relative standard deviation, RSD), respectively. The established method has been successfully applied to a bioequivalence study of two dirithromycin formulations for 18 healthy volunteers.
Interactions of macrolide antibiotics (Erythromycin A, roxithromycin, Erythromycylamine [Dirithromycin], and azithromycin) with phospholipids: computer-aided conformational analysis and studies on acellular and cell culture models
Toxicol Appl Pharmacol 1999 Apr 15;156(2):129-40.PMID:10198278DOI:10.1006/taap.1999.8632.
The potential of 14/15 membered macrolides to cause phospholipidosis has been prospectively assessed, and structure-effects examined, using combined experimental and conformational approaches. Biochemical studies demonstrated drug binding to phosphatidylinositol-containing liposomes and inhibition of the activity of lysosomal phospholipase A1 toward phosphatidylcholine included in the bilayer, in close correlation with the number of cationic groups carried by the drugs (erythromycin A Erythromycylamine Erythromycylamine < azithromycin (roxithromycin could, however, not be studied in detail due to intrinsic toxicity). The difference between Erythromycylamine and azithromycin was accounted for by the lower cellular accumulation of Erythromycylamine. In parallel, based on a methodology developed and validated to study drug-membrane interactions, the conformational analyses revealed that erythromycin A, roxithromycin, Erythromycylamine, and azithromycin penetrate into the hydrophobic domain of a phosphatidylinositol monolayer through their desosamine and cladinose moieties, whereas their macrocycle is found close to the interface. This position allows the aminogroups carried by the macrocycle of the diaminated macrolides (Erythromycylamine and azithromycin) to come into close contact with the negatively charged phosphogroup of phosphatidylinositol, whereas the amine located on the C-3 of the desosamine, common to all four drugs, is located at a greater distance from this phosphogroup. Our study suggests that all macrolides have the potential to cause phospholipidosis but that this effect is modulated by toxicodynamic and toxicokinetic parameters related to the drug structure and mainly to their cationic character.
Quantitative analysis of Erythromycylamine in human plasma by liquid chromatography-tandem mass spectrometry and its application in a bioequivalence study of dirithromycin enteric-coated tablets with a special focus on the fragmentation pattern and carryover effect
J Chromatogr B Analyt Technol Biomed Life Sci 2014 Feb 1;947-948:156-63.PMID:24424301DOI:10.1016/j.jchromb.2013.12.019.
A liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of Erythromycylamine, which is the predominant active metabolite of dirithromycin in human plasma. After solid-phase extraction, the analyte and internal standard (IS) were separated by using an isocratic mobile phase consisting of 20 mM ammonium acetate (pH 3.9, adjusted with formic acid)-acetonitrile (75:25, v/v) on a Phenyl-Hexyl column (150 × 2.1 mm, 3 μm) and then analyzed in positive ion mode under electrospray ionization. Azithromycin was selected as the IS because it has the most similar mass spectrometric and chromatographic behaviors to the analyte. The respective multiple reaction monitoring (MRM) transitions, m/z 368.5>83.2 for Erythromycylamine and m/z 375.4>115.2 for IS were chosen to achieve high sensitivity and selectivity in determination. A more acidic mobile phase (pH 3.9) than those of previous reports and a special needle wash (ethylene glycol-acetonitrile-water, 50:30:20, v/v/v, adjusted to pH 3.9 using formic acid) were used to eliminate the carryover effects of the two macrolides. The method exhibited a linear dynamic range of 0.5-440.0 ng/mL for Erythromycylamine in human plasma (r=0.9999). The lower limit of quantification (LLOQ) and limit of detection (LOD) were 0.5 and 0.05 ng/mL, respectively. The mean extraction recoveries were higher than 94.0% for the analyte and IS. The intra- and inter-day precisions ranged from 1.4 to 5.4% and from 1.6 to 4.0%, respectively. The accuracy varied between 91.2 and 101.2%. The established method was successfully applied to analyze the human plasma samples from 24 healthy subjects in a bioequivalence study of two dirithromycin enteric-coated formulations.
Effects of dirithromycin and Erythromycylamine on human neutrophil degranulation
Antimicrob Agents Chemother 1994 Jul;38(7):1548-54.PMID:7979287DOI:10.1128/AAC.38.7.1548.
Dirithromycin and, to a lesser extent, Erythromycylamine and erythromycin directly induced the release of three intragranular enzymes (lysozyme, lactoferrin, and beta-glucuronidase) from unstimulated human neutrophils. Macrolide-induced enzyme release was dependent upon the incubation time (30 to 180 min) and drug concentration. Dirithromycin was the most effective. At 120 min, release of lysozyme, beta-glucuronidase, and lactoferrin by macrolide (100 micrograms/ml)-treated cells, expressed as a percentage of total enzyme content, was, respectively, 58% +/- 8.3%, 52% +/- 10.7%, and 35% +/- 5.1% (dirithromycin); 42% +/- 3.9%, 28% +/- 5.8%, and 10% +/- 2.2% (Erythromycylamine); and 35% +/- 4.0%, 19% +/- 4.3%, and 10% +/- 5.2% (erythromycin) (mean +/- standard error of the mean of three to eight experiments). The lowest macrolide concentrations which induced significant enzyme release were 10, 100, and 25 micrograms/ml, respectively, for dirithromycin, Erythromycylamine, and erythromycin. Furthermore, we obtained evidence of a link between the prodegranulation effects of dirithromycin and Erythromycylamine and the intragranular location of these drugs. Indeed, cell-associated drug levels increased for up to 60 min and then plateaued and declined substantially. Increasing the pH from 7 to 9 resulted in a parallel increase in drug uptake and the prodegranulation effect. Finally, when macrolide-treated neutrophils were disrupted by sonication and centrifuged, a correlation was found between lysozyme and beta-glucuronidase activities (both granule markers) and pellet-associated macrolide levels. Taken together, our results suggest that dirithromycin and Erythromycylamine concentrate within neutrophil granules and then induce degranulation.