Metrogyl Mechanism of Action

Pharmacology: Mechanism of Action: Metronidazole diffuses into aerobic and anaerobic bacteria equally well, but in the former it remains unchanged while in the latter it is reduced. As a result of biochemical reduction in the cell, the concentration of unchanged drug is reduced and this probably creates a gradient which promotes further uptake of the drug into anaerobic organisms. The selective uptake and specificity of Metronidazole for anaerobes may be because their redox process are different from those aerobes; it has been assumed that the product of reduction of the nitro group of Metronidazole interacts with the DNA with ultimate inhibition of nucleic acid synthesis and subsequent cell death. Moreover Metronidazole has been shown to inhibit DNA synthesis and degrade existing DNA in Clostridium bifermentans.
FC tablet: The nitro group of Metronidazole is reduced in anaerobic bacteria and protozoa by the pyruvate phosphoroclastic reaction, in which the drug acts as a preferential electron acceptor. Oxygen markedly reduces the uptake of Metronidazole in experiments using certain anaerobic protozoa, suggesting that this process depends on reducing power inside the cell.
Oral suspension: The nitro group of Metronidazole accepts electrons from electron-transport proteins and diverts them from normal energy yielding pathways.
Pharmacokinetics: FC tablet: Disposition of Metronidazole in the body is similar for both oral and intravenous dosage forms, with an average elimination half-life in healthy humans of eight hours. The major route of elimination of Metronidazole and its metabolites is via the Urine (60 to 80% of the dose), with fecal excretion accounting for 6 to 15% of the dose. The metabolites that appear in the urine result primarily form side-chain oxidation (1-(beta hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid) and glucuronide conjugation, with unchanged metronidazole accounting for approximately 20% of the total. Renal clearance of metronidazole is approximately 10ml/min/1.73 m². Metronidazole is the major component appearing in the plasma, with lesser quantities of the 2-hydroxymethyl metabolite also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Both the parent compound and the metabolite process In vitro bactericidal activity against most strains of anerobic bacteria and in vitro trichomonacidal activity. Metronidazole appears in cerebrospinal fluid, saliva, and breast milk in concentrations similar to those found in plasma. Bactericidal concentrations of Metronidazole have also been detected in pus form hepatic abscesses. Following administration metronidazole is well absorbed with peak plasma concentrations occurring between one and two hours after administration. Plasma concentrations of Metronidazole are proportional to the administered dose. Oral administration 250 mg, 500 mg, or 2,000 mg produced peak plasma concentrations of bioavailability differences between males and females; however, because of weight differences, the resulting plasma levels in males are generally lower. Decreased renal function does not alter the single dose pharmacokinetics of metronidazole. However, plasma clearance of metronidazole is decreased patients with decreased liver function.
Oral suspension: Metronidazole is completely and promptly absorbed after oral administration. Half- life is about 8 Hrs, and its volume of distribution is approximately that of body water. About 10% of the drug is bound to plasma protein. Metronidazole penetrates well into body tissues and fluids. Therapeutics concentration is also achieved in the cerebrospinal fluid.
Both unchanged metronidazole & several metabolites are excreted in various proportions in the urine after oral administration of the parent compound. The liver is the main site of metabolism and this accounts for over 50% of the systemic clearance of Metronidazole. The 2 principal metabolites result from oxidation of side chains, both have antitrichomonal activity. The major route of elimination of Metronidazole and its metabolites is via the urine (60% to 80% of the dose) with faecal excretion accounting for 6% to 15% of the dose.
Decreased renal function does not alter the single dose pharmacokinetics of Metronidazole. However, plasma clearance of Metronidazole is decreased in patients with decreased liver function.