Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1. Pharmacodynamic properties
Pharmacotherapeutic group: antibacterial antibiotics belonging to the 5-nitroimidazole group, ATC code: J01XD01 — P01AB01 (J: Anti-infectives for systemic use, other antibacterials - imidazole derivatives - P: Anti-protozoals, agents against amoebiasis and other protozoal diseases - nitroimidazole derivatives).
The MIC breakpoints differentiating susceptible from intermediate strains, and intermediate from resistant strains are as follows: S ≤ 4 mg/L and R > 4 mg/L
The prevalence of acquired resistance in certain species can vary geographically and over time. It is therefore useful to have local information on the prevalence of resistance, especially in treating severe infections. These data are only guidelines indicating the probability of susceptibility of a bacterial strain to this antibiotic.
When the variability of prevalence of resistance of a bacterial species is known in France, it is indicated in the table below:
Prevalence of acquired resistance in
Category
France (>10%) (range)
Susceptible species
Gram-negative aerobes
Helicobacter pylori                                    30%
Anaerobes
Bacteroides fragilis
Bifidobacterium                                        60-70%
Bilophila
Clostridium
Clostridium difficile
Clostridium perfringens
Eubacterium                                            20-30%
Fusobacterium
Peptostreptococcus
Porphyromonas
Prevotella
Veillonella
Resistant species
Gram-positive aerobes
Actinomyces
Anaerobes
Moibluncus
Propionibacterium acnes
Antiparasitic activity
Entamoeba histolytica
Giardia intestinalis
Trichomonas vaginalis

Pharmacokinetic Properties

5.2. Pharmacokinetic properties
Absorption
Following oral administration, metronidazole is rapidly absorbed (at least 80% within one hour). Peak plasma concentrations obtained after oral administration are similar to those obtained after IV administration of equivalent doses.
Oral bioavailability is 100%. It is not significantly affected by concomitant intake of food.
Distribution
•   Approximately one hour after a single 500 mg dose, the mean peak plasma concentration is 10 micrograms/mL. After 3 hours, the mean plasma concentration is 13.5 micrograms/mL.
•   The plasma half-life is from 8 to 10 hours.
•   The drug is poorly bound to plasma protein, i.e., below 20%.
•   The apparent volume of distribution is high (approximately 40 L, i.e., 0.65 L/kg).
•   The drug is rapidly and widely distributed, with concentrations close to plasma concentrations, in the lungs, kidneys, liver, skin, bile, CSF, saliva, semen and vaginal secretions.
Metronidazole crosses the placental barrier and is excreted in breast milk.
Biotransformation
Metabolism is mainly hepatic. Two main compounds are formed by oxidation: •    The 'alcohol' metabolite (major metabolite) with antibacterial activity against anaerobes that is approximately 30% that of metronidazole, and an elimination half-life of approximately 11 hours; •    The 'acid' metabolite, in small amounts, with a bactericidal activity of approximately 5% that of metronidazole.
Elimination
High concentrations of metronidazole can be found in the liver and bile. Low concentrations of the drug are found in the colon. Metronidazole is poorly excreted in the faeces. It is mainly eliminated in the urine since metronidazole and its oxidised metabolites, eliminated in the urine, account for approximately 35 to 65% of the administered dose.