Permeability of Nitroimidazoles in Rat Cortex

Meulemans, A.; Vicart, P.; Mohler, J.; Henzel, D.; Vulpillat, M.

doi:10.1159/000238457

Cited by 12 publications

(9 citation statements)

References 15 publications

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“…(26) and the first term was neglected. The parent drug was detected in its free form in the extracellular brain space (16,20,21). This fact was due to the fine tip of the microelectrodes, which were identical to oxygen microelectrodes used in brain physiology studies (17) (24,26,27).…”

Section: Resultsmentioning

confidence: 98%

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Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues

Meulemans

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Hannoun

et al. 1989

Antimicrob Agents Chemother

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A method for determining diffusion coefficients of four antibiotics in extracellular tissue space according to Fick's law is described. This new method was applied to rat brain tissue and to agar. After diffusion of the antibiotic in one axis, the gradient concentration was determined with microvoltammetric electrodes. These microelectrodes (1 micron at the extreme tip) measured the free diffusible form of electroactive antibiotics in the extracellular brain space. Metronidazole, chloramphenicol succinate, cefsulodin, and piperacillin gave diffusion coefficients ranging from 0.1 x 10(-6) to 0.2 x 10(-6) cm2 . s-1 in tissue; chloramphenicol base, which is positively charged, gave a coefficient of 0.04 x 10(-6) cm2 . s-1. The coefficient ranged from 0.6 x 10(-6) to 1.2 x 10(-6) cm2 . s-1 in agar. These coefficients were used to simulate antibiotic concentrations in infectious sites and between capillaries by using a simple model of plane diffusion.

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Section: Resultsmentioning

confidence: 98%

“…The width of 150 to 160 mV. The reproducibility of concentration determinations was less than 5% (16)(17)(18)(19)(20)(21)(22)29). Under the described conditions, the limit of sensitivity was equal to 10 pg-ml-' for the four compounds.…”

Section: Resultsmentioning

confidence: 99%

Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues

Meulemans

Paycha

Hannoun

et al. 1989

Antimicrob Agents Chemother

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“…One relates to leakage of different molecules across the vessel wall and the second is important in view of the potential acute and late effects of various extravasated substances [1] in the development of irreversible brain pathology. Understanding the advanced pathogenesis of neurodegenerative dementia in man has a critical impact on the clinical arena, since dementia connected with neurodegeneration is the main problem in the aging society.…”

Section: Introductionmentioning

confidence: 99%

Pathological Opening of the Blood-Brain Barrier to Horseradish Peroxidase and Amyloid Precursor Protein following Ischemia-Reperfusion Brain Injury

Pluta¹

2005

Chemotherapy

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This study was performed to test the hypothesis that fragments of amyloid precursor protein are able to enter the injured blood-brain barrier (BBB) following brain ischemia. We observed chronic disruption of the BBB after ischemia. The BBB changes did not increase in intensity and frequency with longer periods of recirculation. As an effect of BBB injury, we noted a visible connection of diffuse amyloid plaques with neurovasculature in rats. This pathology appears to have a similar distribution as in Alzheimer’s disease, hippocampal and cortical changes being most severe.

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“…Up to now, voltammetry has been used in the in vivo assay of anticancerous drugs, in permeability studies, and in the measurement of diffusion coefficients of antibiotics [6,9,12]. There are several ad vantages of this method due to the charac teristics of microelectrodes.…”

Section: Discussionmentioning

confidence: 99%

“…These microelec trodes were the same shape as microox ygen or microhydrogen electrodes which have been extensively used in the study of oxygen transport, clearance and blood flow in the rat brain. These captors were located in the extracellular space between capillaries and cells [12][13][14]. In the case of nitrosoureas microelectrodes detected only the parent electroactive free drug which possesses the intact nitroso group [7], Bound drugs were not electroactive.…”

Section: Discussionmentioning

confidence: 99%

Comparative Diffusion Study of Two Nitrosoureas: Carmustine and Fotemustine in Normal Rat Brain, Human and Rat Brain Biopsies

et al. 1991

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In order to assess the apparent diffusion coefficient of two nitrosoureas (carmustine and fotemustine) in the brain, a model of planar diffusion was used in the rat brain and in rat and human brain biopsies. Drugs were deposed on the brain surface at a constant concentration for 30 min. At the end of the diffusion time, the concentration gradient was determined with microelectrodes using voltammetry at 5 different depths in the extracellular space of the gray matter (0–304 μm). Voltammetry with micro-electrodes measured quantitatively intact drug in the brain extracellular space (CV 4% for the 2 drugs) in the range studied. The same procedure was used for human and rat brain biopsies which were held in a small cup. The apparent diffusion coefficients in living animals were 0.49 · 10^––⁶ cm² · s^––1 for carmustine and 0.23 · 10^––6 cm² · s^––1 for fotemustine; in human biopsies, they were 0.84 · 10^––6 cm² · s^––1 for carmustine and 0.37 · 10^––6 cm² · s^––1 for fotemustine. Significant differences in the apparent diffusion coefficients of the drugs were accounted for by the fact that the intracellular penetration of fotemustine was better than that of carmustine.

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Permeability of Nitroimidazoles in Rat Cortex

Cited by 12 publications

References 15 publications

Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues

Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues

Pathological Opening of the Blood-Brain Barrier to Horseradish Peroxidase and Amyloid Precursor Protein following Ischemia-Reperfusion Brain Injury

Comparative Diffusion Study of Two Nitrosoureas: Carmustine and Fotemustine in Normal Rat Brain, Human and Rat Brain Biopsies

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