Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C17H25N3O5S.CO3.2Na |
| Molecular Weight | 489.451 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[Na+].[O-]C([O-])=O.[H][C@]12[C@@H](C)C(S[C@@H]3CN[C@@H](C3)C(=O)N(C)C)=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(O)=O
InChI
InChIKey=SGVRKQURIVADFJ-OBZXMJSBSA-L
InChI=1S/C17H25N3O5S.CH2O3.2Na/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;2-1(3)4;;/h7-12,18,21H,5-6H2,1-4H3,(H,24,25);(H2,2,3,4);;/q;;2*+1/p-2/t7-,8-,9+,10+,11-,12-;;;/m1.../s1
| Molecular Formula | CO3 |
| Molecular Weight | 60.0089 |
| Charge | -2 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C17H25N3O5S |
| Molecular Weight | 383.463 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
| Molecular Formula | Na |
| Molecular Weight | 22.9898 |
| Charge | 1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: https://web.archive.org/web/20161209014344/http://www.ds-pharma.com:80/rd/new_value/meropen.htmlCurator's Comment: description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050706s036lbl.pdf |
Sources: https://web.archive.org/web/20161209014344/http://www.ds-pharma.com:80/rd/new_value/meropen.html
Curator's Comment: description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050706s036lbl.pdf |
Meropenem (generic name: meropenem hydrate) is a carbapenem antibiotic for injection showing a strong antibacterial activity to a wide range of bacteria strains from Gram-positive bacteria, Gram-negative bacteria to anaerobic bacteria. It is used as single agent therapy for the treatment of the following infections: 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. This drug also used in case of Intra-abdominal Infections for the treatment complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species. In addition is used the treatment of bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (b-lactamase and non-b-lactamase-producing isolates), and Neisseria meningitides. 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. Meropenem has significant stability to hydrolysis by β-lactamases, both penicillinases and cephalosporinases produced by Gram-positive and Gram-negative bacteria. Meropenem should not be used to treat methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). Meropenem product with such superior effectiveness and safety has been approved for marketing by 100 countries or more in the world (as of March 2004) since its first launch in Italy in 1994.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2354204 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | MERREM Approved UseTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection, USP (I.V.) and other antibacterial drugs, Meropenem for injection, USP (I.V.) should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Meropenem for injection, USP (I.V.) is useful as presumptive therapy in the indicated condition (e.g. intra-abdominal infections) prior to the identification of the causative organisms because of its broad spectrum of bactericidal activity. For information regarding use in pediatric patients see Indications and Usage (1.1), (1.2) or (1.3); Dosage and Administration (2.3), Adverse Reactions (6.1), and Clinical Pharmacology (12.3). Meropenem for injection (I.V.) is a penem antibacterial indicated as single agent therapy for the treatment of: Complicated skin and skin structure infections (adult patients and pediatric patients 3 months of age and older only). (1.1) Complicated intra-abdominal infections (adult and pediatric patients). (1.2) Bacterial meningitis (pediatric patients 3 months of age and older only). (1.3) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection (I.V.) and other antibacterial drugs, Meropenem for injection (I.V.) should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. 1.1 Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated skin and skin structure infections due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species. 1.2 Intra-abdominal Infections (Adult and Pediatric Patients) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species. 1.3 Bacterial Meningitis (Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of bacterial meningitis caused by Streptococcus pneumoniae ‡, Haemophilus influenzae, and Neisseria meningitidis. ‡ The efficacy of meropenem as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established. Meropenem for injection, USP (I.V.) has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis., 1.1 Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated skin and skin structure infections due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species., 1.2 Intra-abdominal Infections (Adult and Pediatric Patients) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species., 1.3 Bacterial Meningitis (Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of bacterial meningitis caused by Streptococcus pneumoniae ‡, Haemophilus influenzae, and Neisseria meningitidis. ‡ The efficacy of meropenem as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established. Meropenem for injection, USP (I.V.) has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis. Launch Date1996 |
|||
| Primary | MERREM Approved UseTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection, USP (I.V.) and other antibacterial drugs, Meropenem for injection, USP (I.V.) should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Meropenem for injection, USP (I.V.) is useful as presumptive therapy in the indicated condition (e.g. intra-abdominal infections) prior to the identification of the causative organisms because of its broad spectrum of bactericidal activity. For information regarding use in pediatric patients see Indications and Usage (1.1), (1.2) or (1.3); Dosage and Administration (2.3), Adverse Reactions (6.1), and Clinical Pharmacology (12.3). Meropenem for injection (I.V.) is a penem antibacterial indicated as single agent therapy for the treatment of: Complicated skin and skin structure infections (adult patients and pediatric patients 3 months of age and older only). (1.1) Complicated intra-abdominal infections (adult and pediatric patients). (1.2) Bacterial meningitis (pediatric patients 3 months of age and older only). (1.3) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection (I.V.) and other antibacterial drugs, Meropenem for injection (I.V.) should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. 1.1 Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated skin and skin structure infections due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species. 1.2 Intra-abdominal Infections (Adult and Pediatric Patients) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species. 1.3 Bacterial Meningitis (Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of bacterial meningitis caused by Streptococcus pneumoniae ‡, Haemophilus influenzae, and Neisseria meningitidis. ‡ The efficacy of meropenem as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established. Meropenem for injection, USP (I.V.) has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis., 1.1 Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated skin and skin structure infections due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species., 1.2 Intra-abdominal Infections (Adult and Pediatric Patients) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species., 1.3 Bacterial Meningitis (Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of bacterial meningitis caused by Streptococcus pneumoniae ‡, Haemophilus influenzae, and Neisseria meningitidis. ‡ The efficacy of meropenem as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established. Meropenem for injection, USP (I.V.) has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis. Launch Date1996 |
|||
| Curative | MERREM Approved UseTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection, USP (I.V.) and other antibacterial drugs, Meropenem for injection, USP (I.V.) should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Meropenem for injection, USP (I.V.) is useful as presumptive therapy in the indicated condition (e.g. intra-abdominal infections) prior to the identification of the causative organisms because of its broad spectrum of bactericidal activity. For information regarding use in pediatric patients see Indications and Usage (1.1), (1.2) or (1.3); Dosage and Administration (2.3), Adverse Reactions (6.1), and Clinical Pharmacology (12.3). Meropenem for injection (I.V.) is a penem antibacterial indicated as single agent therapy for the treatment of: Complicated skin and skin structure infections (adult patients and pediatric patients 3 months of age and older only). (1.1) Complicated intra-abdominal infections (adult and pediatric patients). (1.2) Bacterial meningitis (pediatric patients 3 months of age and older only). (1.3) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection (I.V.) and other antibacterial drugs, Meropenem for injection (I.V.) should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. 1.1 Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated skin and skin structure infections due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species. 1.2 Intra-abdominal Infections (Adult and Pediatric Patients) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species. 1.3 Bacterial Meningitis (Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of bacterial meningitis caused by Streptococcus pneumoniae ‡, Haemophilus influenzae, and Neisseria meningitidis. ‡ The efficacy of meropenem as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established. Meropenem for injection, USP (I.V.) has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis., 1.1 Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated skin and skin structure infections due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species., 1.2 Intra-abdominal Infections (Adult and Pediatric Patients) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species., 1.3 Bacterial Meningitis (Pediatric Patients 3 Months of age and older only) Meropenem for injection, USP (I.V.) is indicated as a single agent therapy for the treatment of bacterial meningitis caused by Streptococcus pneumoniae ‡, Haemophilus influenzae, and Neisseria meningitidis. ‡ The efficacy of meropenem as monotherapy in the treatment of meningitis caused by penicillin nonsusceptible isolates of Streptococcus pneumoniae has not been established. Meropenem for injection, USP (I.V.) has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis. Launch Date1996 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| In vitro activity of fosfomycin in combination with various antistaphylococcal substances. | 2001 Aug |
|
| [Activity of new fluoroquinolones against clinical isolates of Acinetobacter baumannii]. | 2001 Dec |
|
| Empirical monotherapy with meropenem in serious bacterial infections in children. | 2001 Dec |
|
| MYSTIC program: summary of European data from 1997 to 2000. | 2001 Dec |
|
| MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) conference. Hamburg, Germany, 10 May 2001. | 2001 Dec |
|
| Antibacterial activity of 41 antimicrobials tested against over 2773 bacterial isolates from hospitalized patients with pneumonia: I--results from the SENTRY Antimicrobial Surveillance Program (North America, 1998). | 2001 Feb |
|
| Guidelines and critical pathways for severe hospital-acquired pneumonia. | 2001 Feb |
|
| Rapid antibiotic drug monitoring: meropenem and ceftazidime determination in serum and bronchial secretions by high-performance liquid chromatography-integrated sample preparation. | 2001 Feb 25 |
|
| Nosocomial pneumonia. Diagnostic and therapeutic considerations. | 2001 Jan |
|
| [In vitro and in vivo activities of panipenem against penicillin-resistant Streptococcus pneumoniae]. | 2001 Jul |
|
| Case report: recovery from persistent septicemic melioidosis. | 2001 Jul |
|
| Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems. | 2001 Jul |
|
| Ertapenem: a new carbapenem. | 2001 Jun |
|
| Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey. | 2001 Jun |
|
| Meropenem versus ceftazidime as empirical monotherapy in febrile neutropenia of paediatric patients with cancer. | 2001 Jun |
|
| Antimicrobial susceptibility of Pseudomonas aeruginosa: results of a UK survey and evaluation of the British Society for Antimicrobial Chemotherapy disc susceptibility test. | 2001 Jun |
|
| Continuous beta-lactam antibiotic therapy in a double-lung transplanted patient with a multidrug-resistant Pseudomonas aeruginosa infection. | 2001 Mar 27 |
|
| Antibiotic selective pressure and development of bacterial resistance. | 2001 May |
|
| In vitro activity of garlic oil and four diallyl sulphides against antibiotic-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. | 2001 May |
|
| Characterization of Pseudomonas aeruginosa isolates: occurrence rates, antimicrobial susceptibility patterns, and molecular typing in the global SENTRY Antimicrobial Surveillance Program, 1997-1999. | 2001 May 15 |
|
| Pharmacokinetics of high-dose meropenem in adult cystic fibrosis patients. | 2001 May-Jun |
|
| [A case of eosinophilic pneumonia possibly due to ifenprodil]. | 2001 Nov |
|
| National shortages of antimicrobial agents: results of 2 surveys from the Infectious Diseases Society of America Emerging Infections Network. | 2001 Nov 1 |
|
| Failure of cefotaxime and meropenem to eradicate meningitis caused by an intermediately susceptible Streptococcus pneumoniae strain. | 2001 Oct |
|
| [Susceptibility to penicillin and 13 antimicrobial agents in erythromycin-resistant viridans group streptococci isolated from blood cultures]. | 2001 Sep |
|
| Characterization of paired mucoid/non-mucoid Pseudomonas aeruginosa isolates from Danish cystic fibrosis patients: antibiotic resistance, beta-lactamase activity and RiboPrinting. | 2001 Sep |
|
| Novel mechanism of hydrolysis of therapeutic beta-lactams by Stenotrophomonas maltophilia L1 metallo-beta-lactamase. | 2001 Sep 7 |
|
| Comparative in vitro activity of isepamicin and other antibiotics against gram-negative bacilli from intensive care units (ICU) in Belgium. | 2001 Sep-Oct |
|
| Antimicrobial susceptibilities among clinical isolates of extended-spectrum cephalosporin-resistant Gram-negative bacteria in a Taiwanese University Hospital. | 2002 Jan |
|
| Antibiotic resistance among clinical isolates of Acinetobacter in the UK, and in vitro evaluation of tigecycline (GAR-936). | 2002 Mar |
Sample Use Guides
Adult Patients: The recommended dose of MERREM I.V. is 500 mg given every 8 hours for skin and skin structure infections and 1 gram given every 8 hours for intra-abdominal infections. When treating complicated skin and skin structure infections caused by P.aeruginosa, a dose of 1 gram every 8 hours is recommended.
Pediatric Patients 3 Months of Age and Older: For pediatric patients 3 months of age and older, the MERREM I.V. dose is 10 mg/kg, 20 mg/kg or 40 mg/kg every 8 hours (maximum dose is 2 grams every 8 hours), depending on the type of infection (complicated skin and skin structure, intra-abdominal or meningitis). Pediatric patients weighing over 50 kg should be administered MERREM I.V. at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 gram every 8 hours for intra-abdominal infections and 2 grams every 8 hours for meningitis. MERREM I.V. should be given as intravenous infusion over approximately 15 minutes to 30 minutes or as an intravenous bolus injection (5 mL to 20 mL) over approximately 3 minutes to 5 minutes. There is limited safety data available to support the administration of a 40 mg/kg (up to a maximum of 2 grams) bolus dose.
Route of Administration:
Intravenous
In Vitro Use Guide
Curator's Comment: Meropenem was 4-64 times more active than imipenem against gram-negatives, including Enterobacteriaceae organisms, Pseudomonas aeruginosa, Burkholderia cepacia, Neisseria meningiditis, and Haemophilus influenzae. Imipenem was up to 2-4 times more active than meropenem against some gram-positive cocci, including Enterococcus faecalis. Meropenem, unlike imipenem or ceftazidime, was bactericidal for all strains of Enterobacteriaceae, P. aeruginosa, and gram-positive cocci tested at < or = 8 times the MIC.
Unknown
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 18:16:46 GMT 2023
by
admin
on
Sat Dec 16 18:16:46 GMT 2023
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| Record UNII |
6LJ3NWM7AZ
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| Record Status |
Validated (UNII)
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| Record Version |
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PARENT -> SALT/SOLVATE |
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