What Factors Affect a Sufficient Meropenem Dose?

Meropenem, or transdermal meropenem, is a very wide range of antibacterial and injectable antibiotics used to treat many different infections, including meningitis and pneumonia. It is a beta-lactam antibiotic and belongs to the class of carbapenem.

Chinese name: Meropenem
Foreign name: Meropenem
Other translations: Melopenem

Treatment: Meningitis and pneumonia
Specifications: 0.5g
Package: Molded antibiotic glass bottle
Storage: Keep it tightly closed in a cool, dark and dry place

Meropenem Basic Information

Chinese name

Chinese alias: (-)-(4R, 5S, 6S) -3-[[(3S, 5S) -5- (dimethylcarbamoyl); Menopine; 3-[[5-[(Methylamino) carbonyl] -3-pyrrolidinyl] thio] -6- (1-hydroxyethyl) -4-methyl-7-oxo-1-azabicyclo [3,2,0] heptane- 2-ene-2-carboxylic acid; (-)-(4R, 5S, 6S) -3-[[(3S, 5S) -5- (dimethylcarbamoyl) -3

English name: meropenem

English alias: MEROPENEM, 1 G; MEROPENEM, ANTIBIOTIC FOR CULTURE MEDIA USE ONLY; MeropeneM API; (4R, 5S, 6S) -3-[[(3S, 5S) -5-[(dimethylamino) carbonyl] -3-pyrrolidinyl ] thio] -6-[(1R) -1-hydroxyethyl] -4-methyl-7-oxo-1-azabicycl 0 [3.2.0] hept-2-ene-2-carboxylic acid; Meropenem; MEROPENEM (PATENTED) ; MEROPENAM; MEROPENEM; Meropen; Meronem; MeropeneM Crude; SM 7338; MEROPENEM, USP; Merrem; (1'R, 3'S, 5'S, 4R, 5S, 6S) -3- (5-DIMETHYLCARBAMOYL-PYRROLIDIN-3-YLSULFANYL) -6- (1-HYDROXY-ETHYL) -4-METHYL-7-OXO-1-AZA-BICYCLO [3.2.0] HEPT-2-ENE-2-CARBOXYLIC ACID; MEROPENEM FOR INJECTION; (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;

CAS number: 96036-03-2

Molecular formula: C ₁₇ H ₂₅ N ₃ O ₅ S

Molecular weight: 383.46300

Exact mass: 383.15100

PSA: 135.48000

Physical and chemical properties of meropenem

Density: 1.42 g / cm3

Boiling point: 627.4ºC at 760 mmHg

Flash point: 333.2ºC

Refractive index: 1.639

Meropenem Safety Information

Customs code: 2933990090

Danger category code: R36 / 37/38

Safety instructions: 26-37 / 39

Dangerous goods mark: Xi ^[1]

Meropenem uses

Meropenem is an anti-infective drug that is suitable for infections in adults and children caused by single or multiple bacteria that are sensitive to meropenem. The hospital's first choice for severe infections, mixed infections with G-bacteria, multi-drug resistant bacteria infections, and enzyme-producing bacteria infections. Pneumonia includes nosocomial acquired pneumonia, urinary tract infections, gynecological infections (such as endometritis and pelvic inflammatory disease), skin and soft tissue infections, meningitis, and sepsis.

Meropenem pharmacological action

Meropenem is a synthetic broad-spectrum carbapenem antibiotic that produces antibacterial effects by inhibiting the synthesis of bacterial cell walls.

Meropenem Penetrates the cell wall of most Gram-positive and negative bacteria to reach its target of penicillin-binding protein (PBPS). In addition to metal -lactamase, it has strong stability to the hydrolysis of most -lactamase (including penicillinase and cephalosporinase produced by gram-positive and gram-negative bacteria) . Meropenem should not be used to treat methicillin-resistant staphylococcal infections, and sometimes cross-resistant to other carbapenem-resistant strains. In vitro tests have shown that for some isolated strains of Pseudomonas aeruginosa, the combination of meropenem and aminoglycoside antibiotics can produce a synergistic effect ^[2] .

Meropenem Preparation

Meropenem method

Method name: Determination of Meropenem-High Performance Liquid Chromatography

Scope of application: This method uses high performance liquid chromatography to determine the content of meropenem (C17H25N3O5S · 3H2O).

This method is applicable to meropenem.

Principles of the method: The test product is made into a mobile phase solution, which is subjected to chromatographic separation using a high performance liquid chromatograph. The absorption value of Meropenem is measured at a wavelength of 220 nm using an ultraviolet absorption detector, and the content is calculated.

Reagent: 1. Acetonitrile

2. 0.3% triethylamine solution

Equipment: 1. Instrument

1.1 HPLC

1.2 Column

Octylsilane-bonded silica gel is used as a filler. The resolution of the meropenem peak and the meropenem ring-opening peak should meet the requirements.

1.3 UV absorption detector

Chromatographic conditions

2.1 Mobile phase: 0.3% triethylamine solution acetonitrile = 100 7,

2.2 Detection wavelength: 220nm

2.3 Column temperature: room temperature

Sample preparation:

0.3% triethylamine solution

Take 3.0 mL of triethylamine, dilute to 900 mL with water, adjust the pH to 5.0 with phosphoric acid solution (1 10), and dilute to 1000 mL with water.

2. Weigh the test product

Accurately weigh the appropriate amount of this product.

3. Preparation of reference solution

Accurately weigh the appropriate amount of meropenem, add the mobile phase to dissolve and make a solution containing 0.5mg per 1mL, and shake to obtain.

4. Preparation of test solution

After dissolving the test sample and the mobile phase, a solution containing 0.5 mg per 1 mL is prepared and shaken to obtain.

Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weight taken. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards.

Operation steps: Precisely draw 10 L of each of the reference solution and the test solution into a high-performance liquid chromatograph, measure the absorption value of Meropenem with a UV absorption detector at a wavelength of 220 nm, and calculate its content ^[3] .

Meropenem experimental conclusions

In vitro tests and clinical infection applications have shown that meropenem is active against most of the following microorganisms:

Inhibit cell wall synthesis 1. Gram-positive aerobic bacteria: Streptococcus pneumoniae (excluding penicillin-resistant strains), Streptococcus grass green.

2. Gram-negative aerobic bacteria: E. coli, Haemophilus influenzae (-lactamase positive strain and -lactamase negative strain), Klebsiella pneumoniae, Pseudomonas aeruginosa, and meningitis Thurium.

3. Anaerobic bacteria: B. fragile, B. polymorpha, and digestive streptococcus.

Meropenem exhibits in vitro antibacterial activity against the following microorganisms, but its clinical significance is unknown:

1. Gram-positive aerobic bacteria: Staphylococcus aureus (-lactamase positive strain and -lactamase negative strain), Staphylococcus epidermidis (-lactamase positive strain and -lactamase negative strain) (Note: those who are resistant to methicillin / oxacillin in staphylococci should also be considered to be resistant to meropenem.)

2. Gram-negative aerobic bacteria: Acinetobacter, Aeromonas hydrophila, Campylobacter jejuni, Citrobacter aeruginosa, Citrobacter freundii, Enterobacter cloacae, Haemophilus influenzae (resistant to ampicillin Drug strains and -lactamase negative strains), Moraxella catarrhalis (-lactamase positive strains and -lactamase negative strains), Morgan morganella, Proteus mirabilis, Proteus common, Salmonella, Serratia marcescens, Shigella, etc.

3. Anaerobic bacteria: Bacteroides jejuni, B. ovum, B. morphogenes, B. urealyticum, B. ordinary bacteria, Clostridium difficile, Clostridium perfringens, Eubacteria tarda, Clostridium, Porphyromonas glycerolyticus, Propionibacterium acnes, etc.

Meropenem Toxicology Study

Genotoxicity: Bacterial reverse mutagenicity test, Chinese hamster ovary cell HGPMT test, human lymphocyte gene culture test, and mouse micronucleus test results all found no potential mutagenicity.

staphylococcus Reproductive toxicity: Rats were given meropenem at a dose of 1000 mg / kg / d and cynomolgus monkeys at a dose of 360 mg / kg / d (compared to AUC, equivalent to 1.8 and 3.7 times the human exposure at a 1-gram dose every 8 hours, respectively), No reproductive toxicity, no damage to fertility and fetuses, but rat dose 250mg / kg / d (compared to AUC, respectively equivalent to 0.4 times the human exposure at a dose of 1g every 8 hours) At that time, there was a slight abnormal change in fetal weight.

Meropenem pharmacokinetics

The peak plasma concentration of meropenem in a single intravenous bolus within 5 minutes of healthy volunteers was: 52 mg / ml in the 500 mg dose group and 112 mg / ml in the 1 g dose group; 1 g of meropenem was administered intravenously 2 minutes, 3 minutes, and 5 minutes later, The obtained peak plasma concentrations were 110, 91, and 94 mg / ml, respectively. After 500 hours of intravenous infusion of 500 mg of meropenem, the concentration of meropenem in plasma was 1 mg / ml. Volunteers with normal renal function given different doses of meropenem at three-hour intervals showed no accumulation. Volunteers with normal renal function received intravenous meropenem with a half-life t1 / 2 of approximately one hour. Twelve hours after intravenous injection of meropenem, approximately 70% of meropenem was excreted from the urine as a prototype, and urine was almost undetectable after 12 hours. Intravenous injection of 500 mg of meropenem, the concentration of meropenem in urine was 10 mg / ml, and maintained for more than 5 hours. Healthy volunteers were given 500 mg of meropenem every 8 hours or 1 g of meropenem 6 hours. No meropenem in plasma and Accumulated in urine. Meropenem penetrates well into most body fluids and tissues including bacterial meningitis patients' cerebrospinal fluid to reach effective concentrations.

Children: The pharmacokinetic parameters are similar to those of adults. The half-life t1 / 2 of meropenem in children under 2 years old is about 1.5 to 2.3 hours, and the pharmacokinetic parameters show a good linear relationship within the range of 10 to 40 mg / kg.

Experimental hamster

Patients with renal insufficiency: Plasma clearance of meropenem is related to creatinine clearance, and dose adjustment is necessary for patients with renal impairment.

Elderly patients: Pharmacokinetic studies show that meropenem plasma clearance decreases with age and decreases in creatinine clearance.

Patients with liver disease: Pharmacokinetic studies have shown that liver disease has no effect on the pharmacokinetic parameters of meropenem.

Meropenem drug use

Meropenem indications

Meropenem is suitable for the following infections in adults and children caused by single or multiple susceptible bacteria:

Endometritis

Pneumonia (including nosocomial pneumonia); urinary tract infections; gynecological infections: such as endometritis and pelvic inflammatory disease; skin and soft tissue infections; meningitis;

Chemical formula Empirical treatment. For adult patients with granulocytopenia and fever, this product can be used alone or in combination with antiviral or antifungal drugs.

Meropenem is used alone or in combination with other antimicrobial agents to treat multiple bacterial infections.

For infants with neutropenia or primary and secondary immunodeficiency, there is currently no experience with this product.

Meropenem dosage

Dosage:

Adults: The dosage and time interval should be determined according to the type of infection, the severity of the infection and the specific circumstances of the patient. The recommended daily doses are as follows:

Pneumonia, urinary tract infection, gynecological infection (such as endometritis), skin or soft tissue infection, administered every 8 hours, 500 mg each time, intravenously.

For patients with acquired pneumonia, peritonitis, and neutropenia in patients with combined infection and sepsis, the drug is administered every 8 hours, 1 g each time, and administered intravenously.

Meropenem For meningitis patients, it is recommended to administer 2g every 8 hours.

Children: Children aged 3 months to 12 years old, according to the severity of the infection type, the sensitivity of pathogens and the specific conditions of the patient, children are required to be administered at a dose of 10-20 mg / kg every 8 hours, weighing more than 50 kg It is administered as an adult dose. For the treatment of children with meningitis, the dose is 40mg / kg every 8 hours. There is currently no experience with children with renal insufficiency.

Infants: Infants and young children under 3 months of age, the efficacy and tolerability of this product are not clear. Therefore, meropenem is not recommended for infants and young children under 3 months of age. For treatment.

Patients with a creatinine clearance of less than 51 ml / min should reduce the dose as specified below.

Table 1 Dose adjustment for adults with renal insufficiency

Creatinine clearance (ml / min)

Dose (unit dose 500mg, 1g, 2g)

Time interval (hr)

26 ~ 50

1 unit dose

Every 12 hours

10 ~ 25

1/2 unit dose

Every 12 hours

1/2 unit dose

Every 24 hours

Meropenem for injection

usage:

Meropenem intravenous bolus time should be greater than 5 minutes, intravenous drip time should be greater than 15-30 minutes. Meropenem bolus should be prepared with sterile water for injection (250mg per 5ml) at a concentration of about 50mg / ml.

Meropenem intravenous infusion can be formulated with water for injection or other suitable liquids first, and then diluted to 50 ~ 200ml with a suitable liquid.

Meropenem can be dissolved with the following infusion solutions: 0.9% sodium chloride solution, 5% or 10% glucose solution, 5% glucose solution (sodium bicarbonate concentration 0.02%), 0.9% sodium chloride solution and 5% glucose solution, 5% Glucose solution (sodium chloride concentration 0.225%), 5% glucose solution (potassium chloride concentration 0.15%), 25% or 10% mannitol solution.

Meropenem should not be used in combination with other drugs.

Meropenem notes

Skin test 1. Use with caution in patients with allergic infections of carbapenem antibiotics, penicillins or other beta-lactam antibiotics.

2. Dosage adjustment is not necessary for patients with liver dysfunction, and patients' liver function should be carefully monitored.

3. This product is not recommended for methicillin-resistant Staphylococcus infections.

Skin test for penicillin allergies

4. The use of antibiotics may cause mild to life-threatening pseudomembranous colitis. Patients with diarrhea or increased abdominal pain after using meropenem should be diagnosed as having pseudomembranous colitis caused by Clostridium difficile, and other factors should also be carefully considered.

5. In the treatment of Pseudomonas aeruginosa and other Pseudomonas infections, drug sensitivity tests should be routinely performed.

6. When combined with meropenem and potentially nephrotoxic drugs, it should be noted that this product can be removed by hemodialysis. If the condition requires continuous use of this product, it is recommended to give a full amount according to the condition after hemodialysis to achieve an effective plasma concentration ; For patients with peritoneal dialysis, there is currently no experience using this product.

7. Meropenem should not be frozen. Shake well before use; use this product once after preparation.

8. Keep out of reach of children.

9. This product is incompatible with drugs such as zidovudine, ondansetron, multivitamins, doxycycline, diazepam, calcium gluconate, and acyclovir.

Meropenem adverse reactions

Serious adverse reactions are rare, and the following adverse reactions were seen in clinical trials:

1. Allergic reactions: mainly allergic reactions such as rash, pruritus, and drug fever; occasional anaphylactic shock.

Meropenem 2. Digestive system: gastrointestinal symptoms such as diarrhea, nausea, vomiting, and constipation.

3. Liver: occasional abnormal liver function, cholestasis type jaundice, etc.

4, kidney: occasional dysuria and acute renal failure.

5. Central nervous system: occasional insomnia, anxiety, blurred consciousness, dizziness, nervousness, paresthesia, hallucinations, depression, cramps, disturbances of consciousness and other central nervous system symptoms. It has been reported abroad that seizures can be induced even after administration.

6, blood system: occasional bleeding symptoms such as gastrointestinal bleeding, nosebleeds and abdominal hemorrhage.

7. Injection can cause local pain, swelling and induration, and severe cases can cause thrombophlebitis.

Contraindications to meropenem

Those who are allergic to this product are prohibited.

Meropenem medications for pregnancy

Pregnant women should not use this product unless it can be proven that the effects of the drug on the fetus outweigh the disadvantages; breastfeeding women are not recommended to use this product unless it is proven that the effects of the drug on the infants outweigh the disadvantages.

Meropenem for children

The safety and effectiveness of this product for infants under 3 months have not been established.

Meropenem medication for elderly patients

It is not necessary to adjust the dosage for elderly people with normal renal function or creatinine clearance greater than 50ml / min.

Meropenem drug interactions

1. Combination of probenecid and meropenem can competitively activate renal tubular secretion and inhibit renal excretion, which leads to prolonged clearance half-life of meropenem and increase of blood drug concentration. Therefore, combination of meropenem and probenecid is not recommended.

Adverse reactions

2. This product is used with typhoid vaccine, which may interfere with the immune response of typhoid vaccine.

3. It has been reported that the combination of antiepileptic drugs and this product can reduce the plasma concentration of antiepileptic drugs.

Overdose This product has not been reported in the literature. If overdose occurs during the treatment, especially for patients with impaired renal function, the drug should be discontinued and symptomatic supportive treatment should be performed. Hemodialysis can effectively remove this product ^[4] .