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Meropenem (formerly known as SM-7338; SM7338; ICI194660; Vabomere; Merrem), a beta-lactam of the carbapenem class, is an ultra-broad-spectrum injectable β-lactam antibiotic used to treat a wide variety of infections. Meropenem has been shown to inhibit penicillinase-negative, -positive and methicillin-susceptible staphylococci. Meropenem has an antibacterial spectrum which is broadly similar to that of imipenem but, whilst slightly less active against staphylococci and enterococci, it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae and Haemophilus influenzae. Meropenem demonstrates antagonism with several other beta-lactams against strains producing Type I cephalosporinases.
Physicochemical Properties
| Molecular Formula | C17H25N3O5S |
| Molecular Weight | 383.46 |
| Exact Mass | 383.151 |
| Elemental Analysis | C, 53.25; H, 6.57; N, 10.96; O, 20.86; S, 8.36 |
| CAS # | 96036-03-2 |
| Related CAS # | Meropenem trihydrate;119478-56-7;Meropenem-d6;1217976-95-8 |
| PubChem CID | 441130 |
| Appearance | White to light yellow crystalline powder. |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 627.4±55.0 °C at 760 mmHg |
| Flash Point | 333.2±31.5 °C |
| Vapour Pressure | 0.0±4.2 mmHg at 25°C |
| Index of Refraction | 1.639 |
| LogP | -3.13 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 26 |
| Complexity | 679 |
| Defined Atom Stereocenter Count | 6 |
| SMILES | C(C1=C(S[C@@H]2CN[C@H](C(=O)N(C)C)C2)[C@H](C)[C@@H]2[C@H](C(N12)=O)[C@H](O)C)(=O)O |
| InChi Key | DMJNNHOOLUXYBV-PQTSNVLCSA-N |
| InChi Code | InChI=1S/C17H25N3O5S/c1-7-12-11(8(2)21)16(23)20(12)13(17(24)25)14(7)26-9-5-10(18-6-9)15(22)19(3)4/h7-12,18,21H,5-6H2,1-4H3,(H,24,25)/t7-,8-,9+,10+,11-,12-/m1/s1 |
| Chemical Name | (4R,5S,6S)-3-(((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid |
| Synonyms | Meropenem; ICI 194660; ICI-194660; ICI194660; Merrem; Meropenem anhydrous; Meropenemum; Antibiotic SM 7338; MERONEM; Merrem I.V.; SM-7338; SM 7338; SM7338; Vabomere |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | β-lactam; cell wall synthesis | ||
| ln Vitro |
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| ln Vivo |
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| Enzyme Assay | Meropenem, a new carbapenem, was compared with imipenem and seven other broad-spectrum antimicrobial agents against approximately 1000 clinical isolates. Meropenem was two- to four-fold more active than imipenem against Gram-negative organisms and its spectrum of antimicrobial activity was wider than those of all other drugs tested. However, imipenem was more potent than meropenem against the staphylococci, Streptococcus spp. and enterococci. Many rarely isolated organisms were more susceptible to the carbapenems than to other comparison compounds. All anaerobic bacteria were inhibited by meropenem at less than or equal to 8 mg/l and 50% of strains were inhibited by 0.25 mg/l. Meropenem MICs were not significantly influenced by high inocula and the drug was generally bactericidal. Strains producing various beta-lactamases remained susceptible to meropenem but some isolates producing high levels of chromosomally-mediated enzymes showed an inoculum effect only at 10(7) cfu/ml. Meropenem demonstrated antagonism with several other beta-lactams against strains producing Type I cephalosporinases. Susceptibility tests performed on agar and in broth produced very similar meropenem results. Imipenem and meropenem shared a high degree of cross-susceptibility as measured by dilution test methods. Disc diffusion (10-micrograms disc) regression-line correlations with meropenem MICs are reported with two possible sets of interpretive criteria, using meropenem breakpoints of less than or equal to 2 and less than or equal to 4 mg/l[J Antimicrob Chemother.1989 Sep;24 Suppl A:9-29]. | ||
| Cell Assay | Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro against almost all clinically significant aerobes and anaerobes. Its high activity is explained by ease of entry into bacteria combined with good affinity for essential penicillin binding proteins, including those associated with cell lysis. Breadth of spectrum is due, in part, to stability to all serine-based beta-lactamases, including those which hydrolyse third-generation cephalosporins. Meropenem has an antibacterial spectrum which is broadly similar to that of imipenem but, whilst slightly less active against staphylococci and enterococci, it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae and Haemophilus influenzae. Amongst common human pathogens, only methicillin-resistant staphylococci and Enterococcus faecium are uniformly resistant to meropenem. The meropenem MICs for penicillin-resistant Streptococcus pneumoniae are higher than for penicillin-susceptible strains but the organisms remain susceptible. Clinical susceptibility in vitro to meropenem is defined by MICs of < or = 4 mg/L, intermediate susceptibility by MICs of 8 mg/L and MICs of > or = 16 mg/L define resistance; equivalent figures for zones of growth inhibition are > or = 14 (susceptible), 12-13 (intermediate) and < or = 11 (resistant) mm. Studies in guinea pig models of systemic infection and infections localised to the lungs, urinary tract and the central nervous system, some of which used immunocompromised animals, confirm the potential of meropenem demonstrated in vitro. These factors, combined with the human plasma, tissue or urinary concentrations of meropenem which exceed modal MICs for the pathogens isolated in clinical trials for most or all of the recommended 8 h dosing interval, predict that meropenem should be efficacious in the treatment of infections at many body sites [1]. | ||
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Approximately 70% of the intravenously administered dose is recovered as unchanged meropenem in the urine over 12 hours, after which little further urinary excretion is detectable. Approximately 70% of the intravenously administered dose is recovered as unchanged meropenem in the urine over 12 hours, after which little further urinary excretion is detectable. Urinary concentrations of meropenem in excess of 10 ug/mL are maintained for up to 5 hours after a 500 mg dose. Meropenem is distributed into most body tissues and fluids, including bronchial mucosa, lung, bile, gynecologic tissue (endometrium, myometrium, ovary, cervix, fallopian tube), muscle, heart valves, skin, interstitial and peritoneal fluid, and CSF. Plasma protein binding is approximately 2%. The drug is partially metabolized to at least one microbiologically inactive metabolite. About 70% of an IV dose is eliminated in urine as unchanged drug by tubular secretion and glomerular filtration. At the end of a 30 minute intravenous infusion of a single dose of Meropenem for injection (IV) in healthy volunteers, mean peak plasma concentrations of meropenem are approximately 23 ug/mL (range 14-26) for the 500 mg dose and 49 ug/mL (range 39-58) for the 1 g dose. A 5-minute intravenous bolus injection of Meropenem for injection (IV) in healthy volunteers results in mean peak plasma concentrations of approximately 45 ug/mL (range 18-65) for the 500 mg dose and 112 ug/mL (range 83-140) for the 1 g dose. Following intravenous doses of 500 mg, mean plasma concentrations of meropenem usually decline to approximately 1 ug/mL at 6 hours after administration. No accumulation of meropenem in plasma was observed with regimens using 500 mg administered every 8 hours or 1 g administered every 6 hours in healthy volunteers with normal renal function. Metabolism / Metabolites Primarily excreted unchanged. There is one metabolite which is microbiologically inactive. There is one metabolite of meropenem that is microbiologically inactive. Biological Half-Life Approximately 1 hour in adults and children 2 years of age and older with normal renal function. Approximately 1.5 hours in children 3 months to 2 years of age. The plasma half-life of meropenem is approximately 1 hour in adults with normal renal function and 1.5 hours in children 3 months to 2 years of age. Plasma half-life is increased and clearance of the drug is decreased in patients with renal impairment. |
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| Toxicity/Toxicokinetics |
Hepatotoxicity Serum aminotransferase elevations have been reported in 1% to 6% of recipients of intravenous meropenem when given for up to 14 days. These elevations are usually transient, mild and asymptomatic; and rarely require dose adjustment. Meropenem has also been linked to rare cases of cholestatic jaundice that usually arises after 1 to 3 weeks of therapy. Immunoallergic features may be present, but are rarely prominent. Autoantibodies are rare. Most cases are mild and self-limited, but at least one instance of vanishing bile duct syndrome related to meropenem therapy has been published (Case 1). Meropenem has not been reported to cause acute liver failure. Likelihood score: D (possible rare cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Although no information is available on the use of meropenem during breastfeeding, milk levels appear to be low and beta-lactams are generally not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with beta-lactams, but these effects have not been adequately evaluated. Vaborbactam, which is available in combination with meropenem in the product Vabomere, has not been studied in nursing mothers, but the combination is expected to have similar concerns as with meropenem alone. ◉ Effects in Breastfed Infants A mother received meropenem 1 gram IV every 8 hours for 7 days while exclusively breastfeeding her newborn. When questioned later, she stated that her infant had no oral thrush, watery diarrhea, or diaper dermatitis that required antifungal therapy during the month following her meropenem therapy. An infant was breastfed (extent not stated) until the 4th month postpartum. At 2 months of age, his mother was given a 2-week course of tobramycin and meropenem (dosage not specified) for a cystic fibrosis exacerbation. The infant displayed no change in stool pattern during the maternal treatment and had normal renal function at 6 months of age. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Approximately 2%. |
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| References |
[1]. J Antimicrob Chemother.1995 Jul;36 Suppl A:1-17; [2]. J Antimicrob Chemother. 1989 Sep;24 Suppl A:9-29; [3]. Pharm Res.2001 Sep;18(9):1320-6. |
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| Additional Infomation |
Meropenem is a carbapenemcarboxylic acid in which the azetidine and pyrroline rings carry 1-hydroxymethyl and in which the azetidine and pyrroline rings carry 1-hydroxymethyl and 5-(dimethylcarbamoyl)pyrrolidin-3-ylthio substituents respectively. It has a role as an antibacterial drug, an antibacterial agent and a drug allergen. It is a carbapenemcarboxylic acid, a pyrrolidinecarboxamide, an alpha,beta-unsaturated monocarboxylic acid and an organic sulfide. Meropenem is a broad-spectrum carbapenem antibiotic. It is active against Gram-positive and Gram-negative bacteria. Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death. In August 2017, a combination antibacterial therapy under the market name vabomere was approved for treatment of adult patients with complicated urinary tract infections (cUTI). Vabomere consists of meropenem and [DB12107] and is intravenously admininstered. The treatment aims to resolve infection-related symptoms and achieve negative urine culture, where the infections are proven or strongly suspected to be caused by susceptible bacteria. Meropenem anhydrous is a Penem Antibacterial. Meropenem is a carbapenem antibiotic with broad spectrum of activity that is administered intravenously and used for severe bacterial infections due to sensitive agents. Meropenem is a common cause of mild transient aminotransferase elevations and can rarely result in clinically apparent, cholestatic liver injury. Meropenem has been reported in Brassica napus with data available. Meropenem is a broad-spectrum carbapenem with antibacterial properties, synthetic Meropenem inhibits cell wall synthesis in gram-positive and gram-negative bacteria. It penetrates cell walls and binds to penicillin-binding protein targets. Meropenem acts against aerobes and anaerobes including Klebsiella, E. coli, Enterococcus, Clostridium sp.. (NCI04) Meropenem Anhydrous is the anhydrous form of meropenem, a broad-spectrum carbapenem with antibacterial properties, synthetic Meropenem inhibits cell wall synthesis in gram-positive and gram-negative bacteria. It penetrates cell walls and binds to penicillin-binding protein targets. Meropenem acts against aerobes and anaerobes including Klebsiella, E. coli, Enterococcus, Clostridium sp.. (NCI04) A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than IMIPENEM, but does not need to be given with an enzyme inhibitor such as CILASTATIN. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Drug Indication For use as single agent therapy for the treatment of the following infections when caused by susceptible isolates of the designated microorganisms: complicated skin and skin structure infections due to Staphylococcus aureus (b-lactamase and non-b-lactamase producing, methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (excluding vancomycin-resistant isolates), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and Peptostreptococcus species; complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species. Also for use in the treatment of bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (b-lactamase and non-b-lactamase-producing isolates), and Neisseria meningitidis. FDA Label Treatment of bacterial sepsis, Treatment of bacterial meningitis Mechanism of Action The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding- protein (PBP) targets. Its strongest affinities are toward PBPs 2, 3 and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2 and 4 of Staphylococcus aureus. The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. Its strongest affinities are toward PBPs 2, 3 and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2, and 4 of Staphylococcus aureus. Bactericidal concentrations (defined as a 3 log10 reduction in cell counts within 12 to 24 hours) are typically 1-2 times the bacteriostatic concentrations of meropenem, with the exception of Listeria monocytogenes, against which lethal activity is not observed. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~260.78 mM) Water : ~77 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (6.52 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6078 mL | 13.0392 mL | 26.0783 mL | |
| 5 mM | 0.5216 mL | 2.6078 mL | 5.2157 mL | |
| 10 mM | 0.2608 mL | 1.3039 mL | 2.6078 mL |