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Meropenem Sale

(Synonyms: 美罗培南; SM 7338) 目录号 : GC14746

美罗培南是一种碳青霉烯类抗菌剂。它对金黄色葡萄球菌和大肠杆菌的 MIC 值为 0.03 mg/L,对白僵菌的 MIC 值大于 256 mg/L。美罗培南对革兰氏阴性菌和革兰氏阳性菌产生的大多数β-内酰胺酶(包括青霉素酶和头孢菌素酶)的水解作用稳定。.

Meropenem Chemical Structure

Cas No.:96036-03-2

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10mM (in 1mL DMSO)
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25mg
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50mg
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100mg
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Sample solution is provided at 25 µL, 10mM.

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实验参考方法

Cell experiment [1]:

Cell lines

Human hepatocellular carcinoma cells

Preparation Method

Depending on the specific established microtiter plate hepatotoxicity assay, HepG2/C3A cells were seeded at a density of 5 × 105 cells/mL in 24-well tissue culture plates. Cells were treated with seven antibiotics at varying concentrations: Ampicillin (430 µM, 2150 µM, and 4300 µM), cefepime (210 µM, 1050 µM, and 2100 µM), cefuroxime (140 µM, 700 µM, and 1400 µM), levofloxacin (18 µM, 90 µM, and 180 µM) , linezolid (44 µM, 220 µM, and 440 µM) , meropenem (130 µM, 650 µM, and 1300 µM), rifampicin (24 µM, 120 µM, and 240 µM) , tigecycline (0.85 µM, 4.25 µM, and 8.5 µM), and vancomycin (0.0069 µM, 0.0345 µM, and 0.069 µM) for 2 × 3 days. The lowest concentrations of the various antibiotics, i.e., the mean plasma level after induction of I.V. therapy (Cmax), as well as the 5-times and 10-times concentrations of Cmax, were analyzed. Whereas antibiotic-free medium or plasma served as a negative control, acetaminophen (APAP, 15.24 mM in medium) was used as a positive control.

Reaction Conditions

130 µM, 650 µM, and 1300 µM; for 2 × 3 days.

Applications

A significant increase in lactate dehydrogenase (LDH) at Cmax was detected after incubation with ampicillin, cefepime, cefuroxime, meropenem, rifampicin, tigecycline, and vancomycin. In particular LDH values increased by more than 50% compared to the negative controls (91 U/L) after treatment with ampicillin, meropenem, and rifampicin at Cmax in medium. The testing of Cmax concentrations of antibiotics in plasma showed that all LDH levels were significantly lower than in healthy plasma after 6 days.

Animal experiment [2]:

Animal models

male Sprague-Dawley rats

Preparation Method

All rats underwent laparotomy with cannulation of biliopancreatic duct. Group 1 received intraductal saline injection. Acute necrotizing pancreatitis was induced in group 2, 3, 4, and 5 by intraductal injection of 3% taurocholate. Group 1 (sham operated) and group 2 were injected with saline of 0.3 mL/kg intraperitoneally (i.p). Group 3 was injected with meropenem 60 mg/kg/d i.p, group 4 with deferoxamine 80 mg/kg/d s.c and group 5 with combination of these 2 agents at the same doses. While meropenem was started 2 hours later, all treatments were started immediately after the induction of pancreatitis.

Dosage form

60 mg/kg/d i.p

Applications

Meropenem treatment reduces secondary pancreatic infections in acute pancreatitis.

References:

Doß S, et al. Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro. Curr Issues Mol Biol. 2022 Oct 3;44(10):4639-4657.
Ateskan U, et al. Deferoxamine and meropenem combination therapy in experimental acute pancreatitis. Pancreas. 2003 Oct;27(3):247-52.

产品描述

Meropenem is a carbapenem antibacterial agent[1]. The MICs of meropenem was 0.03 mg/L against S. aureus and E. coli but > 256 mg/L against C. albicans[2]. It is stable to hydrolysis by most beta-lactamases produced by Gram-negative and Gram-positive bacteria, including penicillinases and cephalosporinases[1].

Meropenem, a carbapenem antibacterial agent, is stable to hydrolysis by most beta-lactamases produced by Gram-negative and Gram-positive bacteria, including penicillinases and cephalosporinases[1]. The MICs of meropenem was 0.03 mg/L against S. aureus and E. coli but > 256 mg/L against C. albicans[2].

In vitro, meropenem has the minimum inhibitory concentration (MIC) values is 128 µg/mL, but meropenem combined with vaborbactam reduced the minimum inhibitory concentration (MIC) values of meropenem by ≥ 64-fold against engineered strains and clinical isolates producing class A serine carbapenemases (e.g. KPC-2, KPC-3, SME-2, NMC-A)[3][4]. The minimum inhibitory concentrations of carvacrol and meropenem on carbapenem-resistant K. pneumoniae (CRKP) strains were detected within a range of 32-128 µg/mL using the broth microdilution method[5]. The MIC90 of meropenem (when tested with a fixed concentration of 8 µg/ml of vaborbactam) for isolates of KPC-positive Enterobacteriaceae was 1 µg/ml, and MIC values ranged from ≤0.03 to >32 µg/ml[6].

In vivo, in fully PTZ (pentylenetetrazol)-kindled mice, intravenous administration of meropenem (500 mg/kg) did not elicit any convulsions in the electroconvulsive shock test with low-intensity stimulus currents[7]. In vivo efficacy test shown that cats were administrated 10 mg/kg q12h meropenem is effected against bacteria with MIC values of 6 µg/ml, 7 µg/ml and 10 µg/ml for IV, IM and SC administration, respectively[8].

References:
[1]Zhanel GG, et al. Imipenem-relebactam and meropenem-vaborbactam: two novel carbapenem-beta-lactamase inhibitor combinations. Drugs. 2018;78(1):65-98.
[2]Yu L, et al. Synergetic Effects of Combined Treatment of Colistin With Meropenem or Amikacin on Carbapenem-Resistant Klebsiella pneumoniae in vitro. Front Cell Infect Microbiol. 2019 Dec 10;9:422.
[3]Hecker SJ, et al. Discovery of a cyclic boronic acid beta-lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases. J Med Chem. 2015;58(9):3682-3692.
[4]Lomovskaya O, et al. Vaborbactam: spectrum of beta-lactamase inhibition and impact of resistance mechanisms on activity in Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61(11):e01443-17.
[5]KÖse EO. In vitro activity of carvacrol in combination with meropenem against carbapenem-resistant Klebsiella pneumoniae. Folia Microbiol (Praha). 2022 Feb;67(1):143-156.
[6]Hackel MA, et al. In Vitro Activity of Meropenem-Vaborbactam against Clinical Isolates of KPC-Positive Enterobacteriaceae. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01904-17.
[7]Suemaru K, et al. 5-Fluorouracil exacerbates cefepime-induced convulsions in pentylenetetrazol-kindled mice. Epilepsy Res. 2019 Nov;157:106195.
[8]Albarellos GA, et al. Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats. J Feline Med Surg. 2016 Dec;18(12):976-980.

美罗培南是一种碳青霉烯类抗菌剂[1]。它对金黄色葡萄球菌和大肠杆菌的 MIC 值为 0.03 mg/L,对白僵菌的 MIC 值大于 256 mg/L[2]。美罗培南对革兰氏阴性菌和革兰氏阳性菌产生的大多数β-内酰胺酶(包括青霉素酶和头孢菌素酶)的水解作用稳定[1]。

在体外,美罗培南的最低抑菌浓度(MIC)值为 128 µg/mL,但美罗培南与伐硼内酰胺联合使用,可使美罗培南对产生 A 类丝氨酸碳青霉烯酶(如 KPC-2、KPC-3、SME-2、NMC-A)的工程菌株和临床分离株的最低抑菌浓度(MIC)值降低≥64 倍[3][4]。使用肉汤微稀释法,检测到香芹酚和美罗培南对耐碳青霉烯类药物的肺炎克氏菌(CRKP)菌株的最小抑菌浓度在 32-128 µg/mL 范围内[5]。美罗培南对 KPC 阳性肠杆菌科细菌分离株的 MIC90(与固定浓度为 8 µg/ml 的伐博巴坦一起测试时)为 1 µg/ml,MIC 值范围从≤0.03 到 >32 µg/ml[6]。

在体内,对完全诱发 PTZ(戊四唑)的小鼠静脉注射美罗培南(500 毫克/千克),在低强度刺激电流的电休克试验中不会引起任何惊厥[7]。体内药效试验表明,给猫每 12 小时注射 10 毫克/千克美罗培南对细菌是有效的,静脉注射、口服和皮下注射的 MIC 值分别为 6 微克/毫升、7 微克/毫升和 10 微克/毫升[8]。

Chemical Properties

Cas No. 96036-03-2 SDF
别名 美罗培南; SM 7338
化学名 (4R,5S,6S)-3-[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
Canonical SMILES CC1C2C(C(=O)N2C(=C1SC3CC(NC3)C(=O)N(C)C)C(=O)O)C(C)O
分子式 C17H25N3O5S 分子量 383.46
溶解度 ≥ 19.15mg/mL in DMSO, ≥ 9.88 mg/mL in Water with ultrasonic 储存条件 Store at RT
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