Serum Concentrations of Metronidazole and Its Main Metabolite in Patients with Active Crohn’s Disease: Correlation with Disease Activity and Therapeutic Efficacy?

Schneider, M; Riemann, J.F.; Laudage, G.

doi:10.1159/000238292

Cited by 5 publications

(2 citation statements)

References 15 publications

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“…4). According to previous reports, concentration of metronidazole reaches 10.62-24.88 µg/ml in serum after a 1,000 mg/day dose [50]. Therefore, our study suggests that the used metronidazole concentration in this study was su cient to reduce side effects and resistance concerns while offering enhanced antiparasitic activity when combined with alloferon.…”

Section: Discussionsupporting

confidence: 64%

Alloferon regulates the growth and movement of Trichomonas vaginalis by altering hydrogenosomes

Jo,

Shin,

Agura

et al. 2024

Preprint

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Background Trichomoniasis infected with Trichomonas vaginalis (T. vaginalis), can cause mild symptoms like itching and burning but can also lead to more serious adverse outcomes. While typically treated with metronidazole, this medication can face resistance from T. vaginalis and some individuals may experience side effects. Hence, the research on effective therapeutic methods is essential to improve traditional therapy for trichomoniasis.Method To investigate the potential of alloferon as a therapeutic agent for parasitic infection, we measured the activity of hydrogenosomes in T. vaginalis using flow cytometric analysis and observed the morphology of hydrogenosomes through a transmission electron microscopy. In addition, the cell cycle of T. vaginalis was assessed using cell cycle analysis. To the synergetic effect of alloferon and metronidazole, the movement of T. vaginalis was observed through a microscopy and video recording.Result T. vaginalis treated with alloferon reduced the activity of its energy-producing organelles, hydrogenosomes and changed structure of hydrogenosome. In addition, alloferon induced cell cycle arrest in the S phase of T. vaginalis, thereby leading to decreased proliferation. While metronidazole alone at its minimum lethal concentration was ineffective, combining it with alloferon, significantly suppressed motility and proliferation in T. vaginalis.Conclusion Alloferon induces decreased growth and movement of T. vaginalis by altering the morphology and size of hydrogenosomes. Our findings suggest that alloferon could be a synergistic agent in combination therapy with metronidazole for trichomoniasis.

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Section: Discussionsupporting

confidence: 64%

Alloferon regulates the growth and movement of Trichomonas vaginalis by altering hydrogenosomes

Jo,

Shin,

Agura

et al. 2024

Preprint

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“…In 10 patients with active Crohn's disease both the serum metronidazole Cmax and the serum concentration of the hydroxy metabolite were propor- tional to the 400 and 1000mg doses administered (Schneider et al 1984). The investigators also suggested a possible correlation between the disease activity index and mean serum drug concentrations.…”

Section: Enteric Diseasementioning

confidence: 97%

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Lau

Lam

Piscitelli

et al. 1992

Clinical Pharmacokinetics

184

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Metronidazole was first introduced for the treatment of trichomoniasis. Its therapeutic use has subsequently been expanded to include amoebiasis, giardiasis and, more recently, anaerobic infections. Most of the early pharmacokinetic studies employed nonspecific assays such as microbiological and chemical assays. These assays were not able to differentiate the parent drug from the metabolites or other interfering substances. Pharmacokinetic data obtained through the use of specific chromatographic techniques provide the basis for this review of recent pharmacokinetic findings concerning metronidazole and other nitroimidazole antibiotics. When given intravenously or orally at usual recommended doses, metronidazole attains concentrations well above the minimum inhibitory concentrations for most susceptible micro-organisms. The drug has an oral bioavailability approaching 100%. Rectal and vaginal administration results in a smaller amount of drug absorption and lower serum concentrations. Metronidazole has limited plasma protein binding but can attain very favourable tissue distribution, including into the central nervous system. The drug is extensively metabolised by the liver to form 2 primary oxidative metabolites: the hydroxy and acetic acid metabolites. The kidney is responsible for the elimination of only a small amount of the parent drug; however, normal excretion of the 2 metabolites is dependent on the integrity of kidney function. The metabolism of metronidazole was found to vary among patient groups. Preterm and term infants have lower total body clearance (CL) and prolonged elimination half-lives. However, children older than 4 years old were observed to have pharmacokinetic parameters similar to those in adults. Reduced CL was also observed in children who are malnourished. Elderly patients have reduced renal excretion of both the parent drug and hydroxy metabolite. Pharmacokinetic parameters in pregnant patients were not significantly different from those in nonpregnant women; however, the drug is distributed into breastmilk and the infant will be exposed to the drug through the nursing mother. Patients undergoing gastrointestinal surgery or having enteric diseases and those who are hospitalised or critically ill also have altered pharmacokinetics. Metabolism of the drug is reduced in patients with liver dysfunction, giving delayed production of metabolites. In contrast, renal failure has little effect on the elimination of the parent drug, but affects the excretion of the metabolites more significantly. Haemodialysis was found to remove a substantial amount of the metronidazole while the effect of peritoneal dialysis was more limited. Energy and protein deficient diets as well as occupational exposure to gasoline did not alter metronidazole pharmacokinetics. However, the effect of alcohol consumption on metronidazole CL requires further study.(ABSTRACT TRUNCATED AT 400 WORDS)

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Steady‐state pharmacokinetics of metronidazole in Crohn's disease

Eradiri

Jamali

Thomson

1987

Biopharm & Drug Disp

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The pharmacokinetics of metronidazole (MTZ) were studied in six Crohn's disease patients after multiple oral daily doses of 250, 500, 750, and 1000 mg day-1. Pharmacokinetic indices were found to be independent of the dose administered. The half-life, volume of distribution and oral clearance of metronidazole were 9.5 +/- 2.1 h, 0.732 +/- 0.094 l kg-1 and 0.921 +/- 0.175 (ml min-1) kg-1 (mean +/- SD), respectively. A strong linear correlation (r = 0.95) was found between the volume of distribution of MTZ and the patients' total body weight. The percentage of dose of metronidazole excreted in urine as the intact drug and metabolites as well as glucuronic acid conjugates ranged from 34.7 +/- 7.4 to 58.9 +/- 5.2. Both plasma and urine data exhibited very large inter-patient variations. However, intra-patient variations were negligible. Strong positive linear correlations were observed between the dose and the areas under the plasma concentration versus time curves, peak plasma concentrations as well as cumulative urinary excretion of the drug and its metabolites. It is concluded that in Crohn's disease, the pharmacokinetics of MTZ and its metabolites are linear and that the drug concentrations are dependent on the total body weight.

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Serum Concentrations of Metronidazole and Its Main Metabolite in Patients with Active Crohn’s Disease: Correlation with Disease Activity and Therapeutic Efficacy?

Cited by 5 publications

References 15 publications

Alloferon regulates the growth and movement of Trichomonas vaginalis by altering hydrogenosomes

Alloferon regulates the growth and movement of Trichomonas vaginalis by altering hydrogenosomes

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Steady‐state pharmacokinetics of metronidazole in Crohn's disease

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