Nitrofurans metabolics

Mechanism of Action A synthetic nitrofuran that inhibits bacterial enzymes involved in carbohydrate metabolism. Therapeutic Effect Inhibits a variety of enzymes. Bactericidal. 

Nitrofurans are metabolized in vivo to reduced forms responsible for the effects exerted upon bacteria. These metabolites inhibit bacterial respiration, glucose metabolism, and ribosomal function, and may damage bacterial DNA. 

Due to the rapid and extensive metabolism of nitrofurans in animals, thermostability studies on residues of the parent compounds are not relevant and not published. Instead, the effect of cooking on the concentrations of both the bound and extractable 3-amino-2-oxazolidinone, tire main furazolidone metabolite, in incurred swine tissues has been investigated (43). Total 3-amino-2-oxazolidinone concentrations were not found to be significantly reduced in liver, kidney, or muscle following frying, grilling, or microwaving. 

Some studies have shown similar metabolism of nitrofurantoin and other (carcinogenic) nitrofurans. Formation of carcinogenic nitrofurantoin metabolites is therefore possible (82). However, a carcinogenic effect has not been proven for nitrofurantoin (83). 

The mechanism of antimicrobial action of the nitrofurans has been extensively studied, but it. still is not fully understood. In addition to their antimicrobial actions, the nitnifu-rans are known to be mutagenic and carcinogenic under ca-tain conditions. It is thought that DNA damage caused b) metabolic reaction prcxlucts may be involved in these cellular effects. 

RC Bender, HE Paul. Metabolism of the nitrofurans II. Incubation of furacin with mammalian tissues. J Biol Chem 191 217—222, 1951. 

Nitrofurantoin is a synthetic nitrofuran that is bacteriostatic in low concentrations (5 to 10 mcg/mL) and bactericidal in higher concentrations. Nitrofurantoin may inhibit acetyl-coenzyme A, interfering with bacterial carbohydrate metabolism. It may also disrupt bacterial cell wall formation. 

In addition, nitrofurans may be metabolized to innocuous products which are reincorporated into normal body constituents. 

Under certain circumstances, respective parent antibiotics cannot be targeted as marker residues, and therefore, derivatization and chemical conversion are required. Nitrofurans including furazolidone, furaltadone, nitrofurazone, and nitrofurantoin are metabolized rapidly to 3-amino-2-oxazolidinone (AOZ),... 

Methods for detecting residues of nitrofurans should not aim for the parent drugs because these are rapidly metabolized and do not persist in edible tissues. Nitrofurans form protein-bound metabolites that may persist in tissues for considerable periods after treatment. 

As described above, the nitrofurans used in veterinary practice are quickly metabolized by the animal. 

Metronidazole, at least in part, is subject to reductive metabolism by rat liver microsomes and it is believed that short-lived highly reactive metabolites may be responsible for the genotoxic effects, a phenomenon that might then be extended to other nitroimidazoles. Unfortunately, like the nitrofurans (see Chapter 8), these studies have proved inconclusive. Although the nitroimidazoles are reactive, or are converted to reactive metabolites which then bind covalently to cellular macromolecules, it has not been possible to prove that the bound residues cannot be released as potentially toxic materials following... 

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