Meropenem Trihydrate Chemical Properties

Melting point:

>192°C (dec.)

alpha 

-17～-21゜(d/20℃)(c=0.5,H2O)(calculated on the dehydrous basis)

Boiling point:

627℃

RTECS 

CL5446509

Flash point:

>110°(230°F)

storage temp. 

-20°C

solubility 

Soluble in aqueous solution at approximately 5mg/ml

form 

powder

color 

white to off-white

Merck 

14,5900

InChIKey

DMJNNHOOLUXYBV-PQTSNVLCSA-N

SMILES

C(C1=C([C@H](C)[C@]2([H])[C@@]([H])([C@H](O)C)C(=O)N12)S[C@@H]1CN[C@H](C(=O)N(C)C)C1)(=O)O.O |&1:3,5,7,9,16,19,r|

CAS DataBase Reference

119478-56-7(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26

WGK Germany 

3

HS Code 

2941906000

Meropenem Trihydrate Usage And Synthesis

Chemical Properties

White or slight-yellow crystalline powder LOD ≤0.5% Heavy Metals ≤20 ppm

Uses

Meropenem trihydrate is a carbapenem antibiotic with wide spectrum of antibacterial. It is an ultra-broad spectrum beta-lactam antibiotic and has antibacterial activity against Gram-negative and Gram-positive bacteria as well as anaerobic microorganisms such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter species, Serratia marcescens, Streptococcus pyogenes, Streptococcus agalactiae and Citrobacter sp. Meropenem trihydrate is indicated for the treatment of serious bacterial infection including complicated skin infections, complicated intra-abdominal infections, urinary tract infections, severe pneumonia, broncho-pulmonary infections and bacterial meningitis.

Application

Meropenem trihydrate is 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.
Meropenem trihydrate has also been used in the
antibiotic susceptibility testing of E coli isolates from harbor estuary sediment samples.
in the bacterial killing assay and for screening antibiotic resistance of cystic fibrosis patient′s sputum based Staphylococcus aureus transformed macrophages in phagocyte infection.
for screening Enterococcus faecalis from human bile.

Definition

ChEBI: Meropenem trihydrate is a hydrate. It has a role as an antibacterial drug. It contains a meropenem.

brand name

Merrem I.V. (AstraZeneca).

Antimicrobial activity

The unique side chain at C-2 is associated with increased activity against Gram-negative bacteria, including H. influenzae. It is slightly less active than imipenem against Gram-positive organisms. It is active against anaerobes and more active against some strains that are less susceptible to imipenem. Its excellent activity against Gram-negative organisms is due to high affinity for multiple penicillin-binding proteins. Activity is little affected by inoculum size or the presence of serum. It is bactericidal at concentrations close to the MIC.
Stability to β-lactamases is similar to that of other carbapenems: it is highly resistant to most serine β-lactamases, including extended-spectrum enzymes, but can be hydrolyzed by metallo-β-lactamases and by serine carbapenemases.

General Description

Meropenem trihydrate (MRP) belongs to the carbapenem group of compounds. It is susceptible to degradation at high temperature and humidity. It is soluble in methanol-water or acetone-water combinations. It is used as an antibacterial agent for treating meningitis and pneumonia.

Biological Activity

meropenem trihydrate (sm-7338) is an active ingredient carbapenem antibiotic [1].meropenem trihydrate has shown the potent effect against gram-negative organisms with the mic90 values of 0.03μm, 0.06μm, 0.06μm, 0.12μm,0.25μm, 0.12μm, 0.06μm, 0.12μm and 0.25μm for escherichia coli (30), klebsiella pneumonia(29), klebsiella oxytoca (20), enterobacter aerogenes (14), enterobacter cloacae (29), citrobacter freundii (20), citrobacter diversus (12), proteus mirabilis (15) and morganella morganii (15), respectively. in addition, meropenem trihydrate has also been revealed to restrain gram-positive and anaerobic organisms with the mic90 values of 0.008μm, 4μm and 0.015μm for streptococcus pyogenes (20), viridans group streptococci (27), streptococcus pneumonia (15), respectively. furthermore, meropenem trihydrate has shown the different effect of ph on mic, for example, the mean mic values of 0.06μm and 0.03μm in ph5.5 and ph7.5, respectively [1].

Biochem/physiol Actions

Meropenem trihydrate is an ultra-broad spectrum beta-lactam antibiotic active against both Gram-positive and Gram-negative bacteria.

Pharmacokinetics

C_max 500 mg intravenous (30-min infusion): 23 mg/L end infusion
1 g intravenous (30-min infusion): 49 mg/L end infusion
Plasma half-life: 1 h
Volume of distribution: c. 0.3 L/kg
Plasma protein binding: 2%
Absorption and distribution
Meropenem is not absorbed after oral administration. It penetrates well into most body fluids and tissues, including CSF, achieving concentrations matching or exceeding those required to inhibit most susceptible bacteria. In pediatric patients (1 month to 15 years) with inflamed meninges it achieves CSF levels of 0.9–6.5 mg/L after a single intravenous infusion (40 mg/kg) over 30 min. After a single intravenous dose, the highest mean concentrations of meropenem were found in tissues and fluids at 1 h (0.5–1.5 h) after the start of infusion.
Metabolism and excretion
The mean recovery of unchanged meropenem is approximately 70%. The remainder consists of the microbiologically inactive open-ring form. Renal excretion is greater than 70% of unchanged drug over 12 h. Co-administration with probenecid prolongs the half-life 38%, but peak concentrations are not greatly affected. In patients with renal impairment the dose should be adjusted. Parent drug and metabolite are removed by hemodialysis.

Clinical Use

Meropenem is a second-generation carbapenem that, todate, has undergone the most extensive clinical evaluation.It has recently been approved as Merrem for the treatmentof infections caused by multiply-resistant bacteria and forempirical therapy for serious infections, such as bacterialmeningitis, septicemia, pneumonia, and peritonitis.Meropenem exhibits greater potency against Gram-negativeand anaerobic bacteria than does imipenem, but it is slightlyless active against most Gram-positive species. It is not effectiveagainst MRSA. Meropenem is not hydrolyzed byDHP-I and is resistant to most β-lactamases, including a fewcarbapenemases that hydrolyze carbapenem.

Indications

Intra-abdominal infections
Bacterial meningitis (pediatric patients >3 months)
Complicated skin and skin structure infections

Side effects

Seizures and other CNS adverse experiences have been reported in 0.7% of all adult patients, most commonly those with pre-existing CNS disorders. Pseudomembranous colitis has been reported. Other reactions include diarrhea (4.8%), nausea and vomiting (3.6%), inflammation at the site of injection (2.4%) and headache (2.3%). Moniliasis occurs in 1.9–3.1% of pediatric patients.
Patients with a history of hypersensitivity reactions to other β-lactam agents should be treated cautiously.

Drug interactions

Potentially hazardous interactions with other drugs
Antiepileptics: concentration of valproate reduced - avoid.
Probenecid: avoid concomitant use

Metabolism

Meropenem is more stable to renal dehydropeptidase I than imipenem but undergoes some renal metabolism, and is mainly excreted in the urine by tubular secretion and glomerular filtration. About 70% of a dose is recovered unchanged in the urine over a 12-hour period. Meropenem is reported to have one metabolite (ICI 213689), which is inactive and is excreted in the urine.

References

[1] neu hc1, novelli a, chin nx.in vitro activity and beta-lactamase stability of a new carbapenem, sm-7338.antimicrob agents chemother. 1989 jul; 33(7):1009-18.

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