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Pharmacology: Pharmacodynamics: Metronidazole is an effective, broad-spectrum antiprotozoal and antibacterial drug from the group of nitroimidazole. It is effective for the clinical treatment of patients with pyoinflammatory diseases.
Metronidazole is a nitro imidazole with antiprotozoal and antibacterial actions. It is highly effective against Trichomonas vaginalis, Entamoeba histolytica and Giardia lambia. It has a bactericidal action against pathogenic anaerobic bacteria, particularly Becteroides spp and Fusobacterium spp.
Bacteria inhibited by concentrations of metronidazole as low as 3.1 mcg/ml and killed by concentrations of 6.3 mcg/ml include B. fragilis, B. melaninogenious, Campylobacter fetus, C. perfringes, Eubacterium, Peptococcus, Fusobacterium, Peptostreptococcus and Veilonella spp. In presence of mixed flora (both aerobes and anaerobes), metronidazole acts synergistically with antibiotics effective against common aerobic pathogens.
Metronidazole alone has no direct activity against aerobes and facultative anaerobes.
Pharmacokinetics: Following an intravenous infusion (over 20 minutes) of 500 mg Metronidazole, in patients with anaerobic infections serum concentration achieved were 35.2 mcg/ml at 1 hour, 33.9 mcg/ml at 4 hour, and 25.7 mcg/ml at 8 hours.
The half life following a single intravenous dose is 6-7 hours. Metronidazole is only slightly bound to plasma proteins. It readily penetrates tissues and has a large apparent volume of distribution equivalent to distribution over 70 - 95% body weight. It attains bactericidal concentrations in most tissues and body fluids including brain, CSF, abscess cavities, saliva, bile, vaginal secretions, amniotic fluid and breast milk.
Metabolism: Metronidazole is eliminated in man largely by metabolism resulting from side - chain oxidation, hydroxylation or conjugation of the parent compound. The major metabolic product is 1- (2-hydroxyethyl)-2 hydroxymethyl - 5 nitroimidazole which along with its glucuronide accounts for 40% to 50% of recovered urinary material. The acid and alcohol metabolites of metronidazole are 50% and 30% as active respectively as metronidazole.
Excretion: Over a period of 24 hours urinary recovery of total nitro derivatives accounts for 35% to 65%. Renal clearance is 10.2ml per min/1.75 sq.m. After intravenous administration of a low dose 63% of the total radioactivity is excreted in the urine and 6.2% in the faeces over a 3-days period. In patients with a normal biliary tract, the concentration of metronidazole in gall bladder bile after an intravenous dose of 500mg is significantly higher than in serum.
Influence of Disease on Kinetics: Accumulation of metronidazole has been demonstrated in serum after continual doses in a patient with impaired renal function. Therefore, dosage frequency can be reduced in patients with severe renal insufficiency.
