• Metronidazole

  • Pharmacokinetics

    • Absorption

      • Metronidazole is efficiently absorbed after oral administration, with about 80% bioavailability.¹ 

      • Peak plasma concentrations are reached~1–2 hours following they dose.

      • Oral absorption is not significantly reduced by food (though food may delay the peak slightly).¹ 

        • Because of its high oral bioavailability, oral and IV dosing achieve similar systemic levels, allowing outpatient therapy for serious infections once the patient can tolerate oral intake.²   

    • Distribution

      • Metronidazole distributes widely throughout body tissues and fluids. It has low protein binding (~20% bound)¹, leaving most of the drug free to penetrate tissues.

        • Metronidazole is notably excellent at penetrating anaerobic abscesses and body cavities.

          • Metronidizole achieves therapeutic concentrations in the central nervous system and cerebrospinal fluid (about 43–100% of plasma levels), making it effective for brain abscess and anaerobic meningitis.⁴

        • Metronidizole also crosses the placenta and is excreted into breast milk.

          • Because it distributes into amniotic fluid and the fetus, metronidazole has been scrutinized in pregnancy.⁵

        •  Metronidazole also diffuses into saliva, bile, seminal fluid, and vaginal secretions, reflecting its extensive distribution.

    • Metabolism

      • Metronidazole is primarily and extensively metabolized by the liver.⁶ 

        • Metronidizole is metabolized by the liver to 5 metabolites.

          • The hydroxy metabolite exhibits biological activity of 30%-65% with the longer elimination half-life compared to the parent drug. 

          • About 30–60% of a dose is oxidized by hepatic enzymes⁷  (including CYP2A6 and others) to metabolites such as 2-hydroxymetronidazole and a metronidazole acid derivative.⁸ 

        • Metronidazole undergoes glucuronide conjugation.⁹ 

        • Hepatic metabolism means that severe liver impairment can result in much higher plasma drug levels¹⁰ and a prolonged metronidazole’s half-life.¹¹ 

        • In patients with advanced liver disease (Child-Pugh class C), the elimination half-life can double, and dose reduction (by ~50%) is recommended.¹² 

          • Mild to moderate hepatic impairment does not usually require adjustment, though close monitoring is advised.¹² 

    • Excretion

      • Both metronidazole and its metabolites are excreted mainly in the urine (≈77%), with a smaller portion via feces (~14%).^1,9

        • Unmetabolized metronidazole accounts for about 20% of the excreted drug in urine.⁹

        • Because of the colored metabolites, patients often notice dark or reddish-brown urine while on metronidazole.^13,14   

    • Half-life

      • In healthy adults, the elimination half-life of metronidazole is about 8 hours.¹  The half-life is significantly prolonged in neonates and young infants (e.g. ~23 hours in a 2-month-old, and up to 100 hours in premature neonates.)¹

August, 2025