mereonidazole

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Here is a complete pharmacology summary of Metronidazole (note: you likely meant "metronidazole" - a common 5-nitroimidazole antimicrobial).

Metronidazole

Class: 5-Nitroimidazole | Antiprotozoal + Anaerobic Antibacterial

Mechanism of Action

Metronidazole is a prodrug - it requires reductive activation of its nitro group by susceptible organisms. Anaerobic and microaerophilic pathogens (e.g., T. vaginalis, E. histolytica, G. lamblia, anaerobic bacteria) contain electron transport components (like PFOR - pyruvate-ferredoxin oxidoreductase) with a sufficiently negative redox potential to donate electrons to metronidazole. This generates a highly reactive nitro radical anion that kills organisms via radical-mediated mechanisms that target DNA.

Aerobic organisms cannot activate the drug - hence metronidazole has no significant activity against aerobic or facultatively anaerobic bacteria.

Oxygen competes with metronidazole for electrons, which explains why it does not work against aerobes and why hypoxia enhances activity. - Goodman & Gilman's, Ch. 18

Spectrum of Activity

Category	Organisms
Protozoa	Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia
Anaerobic gram-negative bacilli	Bacteroides fragilis, other Bacteroides spp.
Anaerobic gram-positive bacilli	Clostridium spp. (including C. difficile)
Microaerophilic bacteria	Helicobacter pylori, Campylobacter spp.
NOT active against	Aerobic organisms, nonsporulating gram-positive bacilli

Resistance

Clinical resistance is documented in T. vaginalis, G. lamblia, and anaerobic bacteria. Mechanisms include:

Impaired oxygen-scavenging → elevated local O₂ → decreased drug activation
Lowered levels of PFOR and ferredoxin
Decreased uptake of the drug
Rapid elimination of cytotoxic metabolites before DNA damage can occur

Higher doses can overcome some resistance. - Medical Microbiology 9e, p. 205; Goodman & Gilman's

Pharmacokinetics (ADME)

Parameter	Detail
Routes	Oral, IV, intravaginal, topical
Oral bioavailability	Complete and rapid absorption
Volume of distribution	Approximates total body water
Protein binding	< 20%
t½ (plasma)	~8 hours
Metabolism	Hepatic oxidation of side chains; two main metabolites (hydroxy metabolite t½ ~12 h, ~50% activity)
Excretion	>75% in urine (mostly as metabolites); ~10% unchanged
CSF penetration	Excellent (penetrates most body fluids and tissues)
Placental transfer	Crosses placenta

Urine may turn reddish-brown due to unidentified drug-derived pigments. Metabolism is induced by phenobarbital, rifampin, prednisone, and inhibited by cimetidine. - Goodman & Gilman's, p. 1335

Therapeutic Uses & Dosing

Trichomoniasis

Preferred: 2 g orally as a single dose (both partners treated)
Alternative: 500 mg BID x 7 days
Cures >90% of cases

Amebiasis (symptomatic)

Adult: 750 mg PO TID x 7-10 days (or 500 mg IV q6h)
Child: 35-50 mg/kg/day in 3 divided doses x 7-10 days (max 750 mg/dose)
Always follow with a luminal amebicide (paromomycin, iodoquinol, or diloxanide furoate) - E. histolytica persists after metronidazole alone

Giardiasis

Adult: 250 mg PO TID x 5 days
Child: 15-30 mg/kg/day ÷ TID x 5-7 days (max 750 mg/24 hr)
Note: Not FDA-approved for giardiasis in the US, but widely used

Amebic Liver Abscess / Extraintestinal Amebiasis

750 mg TID x 10 days - cures >95% of uncomplicated liver abscesses
Tinidazole 2 g/day x 5 days is an alternative

Anaerobic Bacterial Infections

Adult (IV): 30 mg/kg/24 hr ÷ q6-8 hr; max 4 g/24 hr; load with 15 mg/kg IV over 1 hour
Infant/Child (PO): 30-50 mg/kg/24 hr ÷ q8h; max 2250 mg/24 hr

Bacterial Vaginosis

500 mg PO BID x 7 days, OR
Vaginal gel 0.75%: 1 applicatorful QHS x 5 days
Vaginal gel 1.3%: single-dose at bedtime

H. pylori Eradication

Part of quadruple regimens (PPI + amoxicillin + metronidazole + bismuth x 14 days)

C. difficile Infection (CDI)

Historically used, but vancomycin is now preferred - clinical data shows vancomycin superior (OR 1.58; 95% CI 1.04-2.40) - Sleisenger & Fordtran's

Neonatal Dosing (Harriet Lane)

PMA	Dose
24-25 wk	7.5 mg/kg q24h
26-27 wk	10 mg/kg q24h
28-33 wk	7.5 mg/kg q12h
34-40 wk	7.5 mg/kg q8h
>40 wk	7.5 mg/kg q6h

Adverse Effects

System	Effect
GI (most common)	Nausea, metallic taste, dry mouth, vomiting, diarrhea, abdominal distress
Neurological	Headache, dizziness, vertigo; rarely encephalopathy, convulsions, ataxia, incoordination
Peripheral nervous system	Numbness, paresthesias (drug must be withdrawn; reversal may be slow/incomplete)
Urological	Dysuria, cystitis, sense of pelvic pressure
Hypersensitivity	Urticaria, flushing, pruritus; rarely Stevens-Johnson syndrome

Drug Interactions

Interaction	Effect
Alcohol	Disulfiram-like reaction: flushing, vomiting, headache, abdominal distress (avoid during and 3 days after therapy)
Disulfiram	Confusional/psychotic states - avoid combination
Warfarin	Metronidazole prolongs prothrombin time - monitor INR
Lithium	Can precipitate CNS signs of lithium toxicity
Phenobarbital/Rifampin	Induce metronidazole metabolism - reduced drug levels
Cimetidine	Inhibits metabolism - increased metronidazole levels
CNS disease	Use cautiously - potential neurotoxicity

Special Populations

Pregnancy: First trimester use is generally not advised; used cautiously later in pregnancy for trichomoniasis (symptomatic cases)
Hepatic impairment: Reduce dose in severe hepatic disease
Breastfeeding: Drug is excreted in breast milk

Formulations Available

Tablets: 250 mg, 500 mg
Capsules: 375 mg
Oral suspension: 50 mg/mL
IV: 5 mg/mL ready-to-use (contains 28 mEq Na/g drug)
Topical gel (0.75%, 1%), lotion (0.75%), cream (0.75%, 1%) - for rosacea
Vaginal gel (0.75%, 1.3%)

Brand names: Flagyl, MetroGel, MetroLotion, MetroCream, Vandazole, Nuvessa, Noritate

Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics, 14e; Katzung's Basic & Clinical Pharmacology, 16e; Medical Microbiology 9e; The Harriet Lane Handbook, 23e; Sleisenger & Fordtran's Gastrointestinal and Liver Disease

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