Pharmacotherapeutic group: Agent against protozoal disease, nitroimidazole derivative.
ATCvet code: QP51AA01.
Pharmacodynamic properties
After metronidazole has penetrated the bacteria the molecule is reduced by the sensitive bacteria (anaerobe). The metabolites that are created have a toxic effect on the bacteria through binding to the bacterial DNA. In general metronidazole is bactericidal for sensitive bacteria in concentrations equal to or a little higher than the minimum inhibiting concentration (MIC).
Minimum Inhibitory Concentrations (MICs) have been determined for metronidazole in European isolates of target bacteria, isolated from dogs with gastrointestinal disease in 2016.
Species | MIC range (μg/ml) | MIC50 (μg/ml) | MIC90 (μg/ml) |
Clostridium spp. (C.difficile & C.perfringens) | 0.5 - 2 | 1 | 1 |
The MICs of the collected pathogens showed mono-modal distribution profiles with good susceptibility towards metronidazole. Clinical breakpoints* for metronidazole are established for anaerobes: susceptible: ≤8 µg/ml; intermediate: 16 µg/ml; resistant: ≥32 µg/ml.
According to these breakpoints no clinical resistant strains of Clostridium spp. pathogens were observed.
*(CLSI, 2017. Performance Standards for Antimicrobial Susceptibility Testing -Twenty-Seventh Edition M100. Clinical and Laboratory Standards Institute (CLSI), Wayne, PA 19087-1898 USA)
Clinically metronidazole does not have any relevant effect on facultative anaerobe, obligate aerobe and microaerophilic bacteria.
Metronidazole is also active in protozoa. In Giardia spp. in particular, metronidazole primarily targets the trophozoites (active replication of the parasite) resulting in their death and by consequence leading to dramatic decrease in cyst shedding.
Pharmacokinetic particulars
After administration of the higher dose (50 mg/day/kg of bw), the absolute bioavailability is 98 % in fasted dog. The mean maximum concentration (Cmax) was 62.4 µg/mL +/- 9.7 (mean +/- SD) in plasma and occurs between 0.25 and 4 hours after dosing (Tmax). Food was shown to decrease the oral bioavailability which remains high in fed dogs with relative F of 81% (with F fasted = 100%). Metronidazole penetrates into the tissues and bodily fluids, such as saliva, milk, vaginal secretions and semen. Metronidazole is metabolised in the liver, by side chain oxidation and glucuronide synthesis. Both metabolites and unchanged drug are eliminated in the urine (mostly) and faeces. Elimination half-life is between 3 to 5 hours.