Pharmacokinetics and Pharmacodynamics of the Nitroimidazole Antimicrobials

@article{Lamp1999PharmacokineticsAP,
  title={Pharmacokinetics and Pharmacodynamics of the Nitroimidazole Antimicrobials},
  author={Kenneth C. Lamp and Collin D. Freeman and Neil E. Klutman and Melinda K. Lacy},
  journal={Clinical Pharmacokinetics},
  year={1999},
  volume={36},
  pages={353-373}
}
Metronidazole, the prototype nitroimidazole antimicrobial, was originally introduced to treat Trichomonas vaginalis, but is now used for the treatment of anaerobic and protozoal infections. The nitroimidazoles are bactericidal through toxic metabolites which cause DNA strand breakage. Resistance, both clinical and microbiological, has been described only rarely.Metronidazole given orally is absorbed almost completely, with bioavailability >90% for tablets; absorption is unaffected by infection… 

Nitroimidazole-induced chronic hepatitis

This is the first chronic hepatitis case to be induced by nitroimidazole-related hepatotoxicity, and there is no literature suggesting chronic hepatitis due to nitroinformatics use, according to this report.

Bioavailability and pharmacokinetics of metronidazole in fed and fasted horses.

Narrow margin of safety was suggested because histological evidence of peripheral neurotoxicity and hepatotoxicity were noted in horses treated with doses as low as 30 mg/kg body weight every 12 h orally for 30 days (White et al., 1996).

Bioavailability File: Metronidazole

Summary Metronidazole is an antimicrobial nitroimidazole derivative, which was originally introduced to treat Trichomonas vaginalis but nowadays is used for the treatment of anaerobic and protozoal

Clinical Pharmacology of Metronidazole in Infants and Children Running title: Metronidazole in infants and children

The aim of this study is to review the metronidazole dosing, efficacy, safety, effects, pharmacokinetics, metabolism, toxicity, treatment, prophylaxis, penetration into the cerebrospinal fluid, treatment of meningitis, in infants and children, and metronIDazole transfer across the human placenta and migration into the breastmilk.

Bioavailability File : Ornidazole

Physicochemical, pharmacological and pharmacokinetic properties in addition to bioavailability of ornidazole are discussed, which are a particular advantage for reducing the dosage frequency and duration of therapy in many of the relevant clinical infections.

A comparison of metronidazole and single-dose ornidazole for the treatment of dientamoebiasis.

It is suggested that single-dose ornidazole may be an important alternative agent for the treatment of dientamoebiasis, because of its longer half-life and fewer side-effects.

Metronidazole Metabolism in Neonates and the Interplay Between Ontogeny and Genetic Variation

The objective of this study was to evaluate the effect of CYP2A6 genetic variation on the pharmacokinetics of metronidazole in a small cohort of preterm neonates.

Distribution of metronidazole in muscle tissue of patients with septic shock and its efficacy against Bacteroides fragilis in vitro.

Pharmacokinetic-pharmacodynamic simulation of metronidazole interstitial concentrations shows a high efficacy of the drug in septic patients.

Pharmacokinetic and Pharmacodynamic Effects of Metronidazole May Account for the Superior Efficacy of Multidose Therapy Among Women With Trichomoniasis.

Two potential effects are suggested which may account for the superior efficacy of multidose MTZ versus single dose among women with trichomoniasis: competition for MTZ and inadequate accumulation of the metabolites of MTZ.
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References

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The traditional dosage recommendation of 500mg every 6h is more than adequate to treat most anaerobic infections and microbiology, and a regimen of500mg every 8h can be expected to maintain serum concentrations above the minimum inhibitory concentrations for most susceptible micro-organisms.

Pharmacokinetics of nitroimidazoles. Spectrum of adverse reactions.

The nature and frequency of adverse reactions to this drug include encephalopathy in a few patients treated with doses between 5 and 10 g daily as an adjunct to radiotherapy, and peripheral neuropathy observed in patients treated for prolonged periods with high doses.

Comparative pharmacokinetics of metronidazole and tinidazole and their tissue penetration.

The slower disposition of OH-metronidazole, which inhibits anaerobic bacteria, prolongs the duration of bioactivity in the body after metronidrazole to that reached by tinidazoles.

Pharmacokinetics and therapeutic efficacy of metronidazole at different dosages.

Metronidazole, a drug effective against certain protozoal and anaerobic infections, was given female patients with Trichomoniasis urogenitalis and the cure rate was 100%.

Pharmacokinetics of Metronidazole as Determined by Bioassay

Blood levels increased progressively for the first few doses and then leveled off, with no significant accumulation occurring between 3 and 7 days, and since the minimum inhibitory concentrations of most anaerobes including Bacteroides fragilis are less than 6 μg/ml, these concentrations should be highly effective therapeutically, even for severe infections.

Pharmacokinetics of intravenous metronidazole at different dosages in healthy subjects.

The findings revealed that the pharmacokinetics of metronidazole and its hydroxy metabolite are altered when higher doses of the drug are given; the metabolic transformation of the parent drug is also expected to be reduced.

Secnidazole. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic use in the management of protozoal infections and bacterial vaginosis.

Available evidence suggests that secnidazole is as efficacious as other 5-nitroimidazoles drugs in the treatment of protozoal infections and bacterial vaginosis and is an attractive alternative to multiple dosage regimens with other drugs in this class.

Pharmacodynamics of metronidazole determined by a time-kill assay for Trichomonas vaginalis

The data suggest that peak metronidazole concentration and/or area under the plasma concentration-versus-time curve are the important pharmacodynamic parameters to be optimized.

Pharmacokinetics of metronidazole and its metabolites in reduced renal function.

In the patients with reduced renal function, the relative contribution of A-M is higher than that of the other two products, and the total body clearance of the unchanged compound was not influenced by reducing renal function.
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