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Details

Stereochemistry ACHIRAL
Molecular Formula C6H8N3O3.Na
Molecular Weight 193.1358
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METRONIDAZOLE SODIUM

SMILES

[Na+].CC1=NC=C(N1CC[O-])[N+]([O-])=O

InChI

InChIKey=LKRWBLLGEAXPRY-UHFFFAOYSA-N
InChI=1S/C6H8N3O3.Na/c1-5-7-4-6(9(11)12)8(5)2-3-10;/h4H,2-3H2,1H3;/q-1;+1

HIDE SMILES / InChI

Description

Metronidazole was synthesized by France's Rhone-Poulenc laboratories and introduced in the mid-1950s under the brand name Flagel in the US, while Sanofi-Aventis markets metronidazole globally under the same trade name, Flagyl, and also by various generic manufacturers. Metronidazole is one of the rare examples of a drug developed as ant parasitic, which has since gained broad use as an antibacterial agent. Metronidazole, a nitroimidazole, exerts antibacterial effects in an anaerobic environment against most obligate anaerobes. Metronidazole is indicated for the treatment of the following infections due to susceptible strains of sensitive organisms: Trichomoniasis: symptomatic, asymptomatic, asymptomatic consorts; Amebiasis: acute intestinal amebiasis (amebic dysentery) and amebic liver abscess; Anaerobic bacterial infections; Intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess; Skin and skin structure infections; Gynecologic infections, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection; Bacterial septicemia; Bone and joint infections, as adjunctive therapy; Central Nervous System infections, including meningitis and brain abscess; Lower Respiratory Tract infections, including pneumonia, empyema, and lung abscess; Endocarditis. Metronidazole is NOT effective for infections caused by aerobic bacteria that can survive in the presence of oxygen. Metronidazole is only effective against anaerobic bacterial infections because the presence of oxygen will inhibit the nitrogen-reduction process that is crucial to the drug's mechanism of action. Once metronidazole enters the organism by passive diffusion and activated in the cytoplasm of susceptible anaerobic bacteria, it is reduced; this process includes intracellular electron transport proteins such as ferredoxin, transfer of an electron to the nitro group of the metronidazole, and formation of a short-lived nitroso free radical. Because of this alteration of the metronidazole molecule, a concentration gradient is created and maintained which promotes the drug’s intracellular transport. The reduced form of metronidazole and free radicals can interact with DNA leading to inhibition of DNA synthesis and DNA degradation leading to death of the bacteria. The precise mechanism of action of metronidazole is unknown. Metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
FLAGYL
Curative
FLAGYL
Curative
FLAGYL

Cmax

ValueDoseCo-administeredAnalytePopulation
12 μg/mL
500 mg single, oral
METRONIDAZOLE plasma
Homo sapiens
25 μg/mL
7.5 mg/kg 4 times / day steady-state, intravenous
METRONIDAZOLE plasma
Homo sapiens
40 μg/mL
2000 mg single, oral
METRONIDAZOLE plasma
Homo sapiens
6 μg/mL
250 mg single, oral
METRONIDAZOLE plasma
Homo sapiens
6.77 μg/mL
250 mg single, oral
METRONIDAZOLE plasma
Homo sapiens
16.54 mg/L
15 mg/kg single, intravenous
METRONIDAZOLE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
75.23 μg × h/mL
250 mg single, oral
METRONIDAZOLE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
8 h
500 mg single, oral
METRONIDAZOLE plasma
Homo sapiens
8 h
2000 mg single, oral
METRONIDAZOLE plasma
Homo sapiens
8 h
250 mg single, oral
METRONIDAZOLE plasma
Homo sapiens
8 h
unknown, oral
METRONIDAZOLE plasma
Homo sapiens
7.76 h
250 mg single, oral
METRONIDAZOLE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
80%
unknown, oral
METRONIDAZOLE plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

PubMed

Sample Use Guides

In Vivo Use Guide
Trichomoniasis: In the Female: One-day treatment − two grams of FLAGYL, given ither as a single dose or in two divided doses of one gram each, given in the same day. Anaerobic Bacterial Infections: In the treatment of most serious anaerobic infections, intravenous metronidazole is usually administered initially. The usual adult oral dosage is 7.5 mg/kg every six hours (approx. 500 mg for a 70-kg adult). A maximum of 4 g should not be exceeded during a 24-hour period. Amebiasis: Adults: For acute intestinal amebiasis (acute amebic dysentery): 750 mg orally three times daily for 5 to 10 days. For amebic liver abscess: 500 mg or 750 mg orally three times daily for 5 to 10 days. Pediatric patients: 35 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days.
Route of Administration: Other
In Vitro Use Guide
Cells incubated with lethal drug (Metronidazole (MTZ)) concentration exhibit unchanged DNA profile, only about 50% of cells are positive for γH2A and lose an ability to attach to a surface after few hours of incubation. It is likely that the early reaction of cells to lethal concentration of MTZ is not primarily initiated by the reaction to DNA damage but rather by the immediate interaction of MTZ with biomolecules where activated MTZ is generated.