The pharmacokinetics of pyridostigmine

Cohan, Stanley; Pohlmann, Juergen L. W.; Mikszewski, Jerold; O'Doherty, Desmond S.

doi:10.1212/wnl.26.6.536

Cited by 56 publications

(23 citation statements)

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“…Quaternary carbamates do not easily pass the blood brain barrier and their effect, therefore, is primarily on the peripheral nervous system. Metabolic and kinetic studies indicate that PB is poorly absorbed from the gut and, in order to produce a pharmacological effect, high levels must be given orally [32,33]. LD 50 of PB tablet was estimated to be 66.9 mg/kg higher than 61.6 mg/ kg reported by Pool and Hane [3] lower than 80 mg/kg reported by McCain et al [2], Latven and Sloane [4].…”

Section: Discussionmentioning

confidence: 90%

Pyridostigmine Bromide and Potassium Iodate: Subacute Oral Toxicity and Stability

Bigoniya¹

2013

J Drug Metab Toxicol

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Subacute toxicity of pyridostigmine bromide (PB) and potassium iodate (PI) tablets upon forty five days administration were assessed by changes in body weight, hematology, serum biochemical parameters and histopathology of rat liver and kidney. LD 50 of PB was estimated to be 66.9 mg/kg. At dose of 45 mg/kg/day showed decrease in body weight and liver weight with cytoplasmic acidophilic bodies and vesicular steatosis signifying hepatocellular injury. Kidney tissue developed neutrophil polymorph infiltration with inflammatory glomerulonephritis, protein casts and glomerulosclerosis. Serum SGOT, SGPT, ALP and lipid profile were elevated. The oral LD 50 of PI was found to be 944.6 mg/kg. PI at 150 mg/kg dose showed anorexia and body weight loss. Serum SGOT, ALP, cholesterol and triglyceride level were elevated at 85 and 150 mg/kg dose and focal area of tubular injury and inflammatory cell infiltration occurred only at 150 mg/kg dose in kidney. The content of PB and PI has been found stable in accelerated (40 ± 2°C/75 ± 5% RH), intermediate (30 ± 2°C/65 ± 5% RH) and long term (30 ± 2°C/65 ± 5% RH) conditions. PB 30 mg/kg/day and PI 85 mg/kg/day doses are safe for rats, which are far in excess of human exposure levels.

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Section: Discussionmentioning

confidence: 90%

Pyridostigmine Bromide and Potassium Iodate: Subacute Oral Toxicity and Stability

Bigoniya¹

2013

J Drug Metab Toxicol

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“…The chemical structure, molecular formula and molecular weight are shown in Figure 1. The literature survey reveals several methods for determination of PB including spectrophotometry [7], HPLC [8][9][10][11], GC [12][13][14][15] and CE [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of three spectrophotometric methods for determination of pyridostigmine bromide in the presence of its alkaline-induced degradation product

et al. 2015

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Three simple, accurate and validated spectrophotometric methods were developed for the determination of pyridostigmine bromide (PB) in presence of its alkaline-induced degradation product, 3-hydoxy-N-methylpyridinium bromide (3-OH NMP) in powder form and in pharmaceutical formulations. Method A, is first derivative method ( 1 D), which is based on measuring the peak amplitude of the first derivative spectra ( 1 D) of PB at 260 nm. Method B, is first derivative of ratio spectra ( 1 DD) which allows the determination of PB at 267.4 nm using (50 µg/mL) of 3-OH NMP as a suitable devisor. Finally, method C depends on mean centering of ratio spectra (MCR) of PB with different concentrations, which were recorded over 200-400 nm and divided by the spectrum of 20 µg/mL of 3-OH NMP as a devisor. The obtained ratio spectra were mean centered and the concentrations of PB were then determined from the calibration graphs obtained by measuring the amplitudes at 338 nm. The proposed methods were successfully applied for assay of PB both in pure form and in pharmaceutical formulations. The proposed methods were validated in compliance with International Conference on Harmonization (ICH) guidelines. The results obtained by the developed methods were statistically compared to those obtained by the reported HPLC method using Fand student's t-tests showing no significant difference regarding both accuracy and precision.

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“…High levels of DEET exposure have been reported to cause spongiform myelinopathy [35]. Because DEET efficiently crosses the dermal barrier [37,17,31] and localizes in dermal fat deposits [5,29], it is possible that DEET could enhance the availability of drugs and toxicants to other organs, including the brain [31].…”

Section: Introductionmentioning

confidence: 99%

“…PII: S0378-4347(00)00407-2 veterans, and permethrin was sprayed against orthropod vectors on the battle dress uniforms [35]. Pyridostigmine bromide has been reported to be absorbed into plasma and excreted in urine following oral or intravenous dose in rat [9,10,17,18,27,29,36], in man [16,24], and in dog [15,28]. Absorption and excretion of DEET and metabolites were rapid after dermal application in human [11,13], in rats [19], and in dogs [14].…”

Section: Introductionmentioning

confidence: 99%

Toxic Interactions of Prophylactic Drugs and Pesticides

Abou‐Donia¹

2003

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Approved for public release; Distribution unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 Words/The goal of the present project is to define the mechanisms of neurotoxic interactions following exposure to pyridostigmine bromide (PB, 0.13, 1.3,13 mg/gk in water, oral), DEET (4.0, 40.0, 400.0 mg/kg in ethanol, dermal), and permethrin (0.013, 0.13, 1.3 mg/kg in ethanol, dermal) in male Sprauge-Dawley rats. The results are summarized below. 1. Combined exposure to the three test compounds for 28 days, alone or with stress produced neuropathological alterations in the brain and hepatic lesions. 2. The same treatments increased the permeability of the blood brain barrier (BBB), as assessed by [ 3 H]hexamethonium iodide uptake and horseradish peroxidase (HRP) staining.3. Specific brain region exhibited decreased activity of AChE and ligand binding of m2 muscarinic acetylcholine receptors. 4. Exposure to DEET alone, or with permethrin significantly increased urinary excretion of 8-hydroxy-2'-deoxyguanosine. 5. Within 30 minutes of dermal application of 400 mg/kg DEET alone, or in combination with 1.3 mg/kg permethrin, 55% DEET and 38% permethrin was absorbed. Distribution of permethrin in tissues was slower than DEET.Combined application to both chemicals increased AUC for DEET but did not affect AUC FlasT . a of permethrin. The goal of this project is to evaluate the possible interaction between DEET, permethrin and pyridostigmine bromide (PB) and the biological and pathological consequences of such interactions. Our standing hypothesis is that combined exposure to a mixture of chemicals would have enhanced, and in some cases deterimental toxicological effects than exposure with single chemical. SUBJECT TERMS B) ApproachWe have been testing the stated hypothesis that interactions between combined chemical exposure would result in greater toxicological and pathological changes, and certain environmental modifying factors such as stress would modulate the toxic effects in combined exposure scenario. In the previous year we have carried out dose-response studies ranging from 0.1-10 x the estimated human exposure on DEET, permethrin and PB. In those studies we carried out neurobehavioral as well as neurochemical assessment following exposure to a single or multiple chemicals (See the manuscripts in Appendix). In the current studies, we have focused on the pathological consequences of sub-chronic exposure to single chemical or combined concurrent exposure. Additionally, we studied the effect of one environmental modifier, stress on the neurotoxicity associated with concurrent exposure to PB, DEET and permethrin. The pathological changes were studied by immunohistochemical evaluation of microtubule-associated protein-2 (MAP-2), glialfibrillary acidic protein (GFAP), and microglial activation by lectin binding. Furthermore, we evaluated the possible mechanism(s) of neurotoxic effects of single or combined exposure by assessing the permeability of blood-brain barrier (BBB) and evaluating 8-hydroxy-2'-deoxyguanosine by ...

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The pharmacokinetics of pyridostigmine

Cited by 56 publications

References 0 publications

Pyridostigmine Bromide and Potassium Iodate: Subacute Oral Toxicity and Stability

Pyridostigmine Bromide and Potassium Iodate: Subacute Oral Toxicity and Stability

Development and validation of three spectrophotometric methods for determination of pyridostigmine bromide in the presence of its alkaline-induced degradation product

Toxic Interactions of Prophylactic Drugs and Pesticides

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