Biodistribution of Radiolabeled Ethanol in Rodents

Gifford, Andrew N.; Espaillat, Mel Pilar; Gatley, S. John

doi:10.1124/dmd.107.020271

Cited by 4 publications

(3 citation statements)

References 27 publications

(25 reference statements)

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“…Information about the total fate of drug-related material and routes of excretion can be obtained from mass balance studies (Park et al, 1997; Schadt et al, 2012). QWBA studies provide the tissue distribution and pharmacokinetics data required for new drug registration and for predicting human exposure to radioactivity during clinical radiolabeled mass balance studies (Gifford et al, 2008; Wang et al, 2011). Both QWBA and mass balance studies are required for regulatory filings of a new drug entity and for projecting tissue dosimetry in human mass balance studies (Scicinski et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Metabolic disposition of the anti-cancer agent [¹⁴C]laromustine in male rats

Nassar

Wisnewski

King³

2015

Xenobiotica

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Laromustine (VNP40101M, also known as Cloretazine) is a novel sulfonylhydrazine alkylating (anticancer) agent. This article describes the use of quantitative whole-body autoradiography (QWBA) and mass balance to study the tissue distribution, the excretion mass balance and pharmacokinetics after intravenous administration of [14C]VNP40101M to rats. A single 10 mg/kg IV bolus dose of [14C]VNP40101M was given to rats. The recovery of radioactivity from the Group 1 animals over a 7-day period was an average of 92.1% of the administered dose, which was accounted for in the excreta and carcass. Most of the radioactivity was eliminated within 48 h via urine (48%), with less excreted in feces (5%) and expired air accounted for (11%). The plasma half-life of [14C]laromustine was approximately 62 min and the peak plasma concentration (Cmax) averaged 8.3 μg/mL The QWBA study indicated that the drug-derived radioactivity was widely distributed to tissues through 7 days post-dose after a single 10 mg/kg IV bolus dose of [14C]VNP40101M to male pigmented Long–Evans rats. The maximum concentrations were observed at 0.5 or 1 h post-dose for majority tissues (28 of 42). The highest concentrations of radioactivity were found in the small intestine contents at 0.5 h (112.137 μg equiv/g), urinary bladder contents at 3 h (89.636 μg equiv/g) and probably reflect excretion of drug and metabolites. The highest concentrations in specific organs were found in the renal cortex at 1 h (28.582 μg equiv/g), small intestine at 3 h (16.946 μg equiv/g), Harderian gland at 3 h (12.332 μg equiv/g) and pancreas at 3 h (12.635 μg equiv/g). Concentrations in the cerebrum (1.978 μg equiv/g), cerebellum (2.109 μg equiv/g), medulla (1.797 μg equiv/g) and spinal cord (1.510 μg equiv/g) were maximal at 0.5 h post-dose and persisted for 7 days. The predicted total body and target organ exposures for humans given a single 100μCi IV dose of [14C]VNP40101M were well within the medical guidelines for maximum radioactivity exposures in human subjects.

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Section: Introductionmentioning

confidence: 99%

Metabolic disposition of the anti-cancer agent [¹⁴C]laromustine in male rats

Nassar

Wisnewski

King³

2015

Xenobiotica

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“…Os 10% restantes são eliminados de forma inalterada pelos pulmões, rins, suor e saliva (Paton, 2005;Gifford et al, 2008).…”

Section: Revisão De Literaturaunclassified

“…Em ratos, a saturação desta biotransformação é de aproximadamente 700 mg/kg/h. O tempo de meia-vida farmacológica após a ministração intravenosa de 250 mg/kg nestes animais é de 30 minutos (Gifford et al, 2008 (Edenberg, 2007;Sloan et al, 2008;Strat et al, 2008 cefaléia pulsante e taquicardia (Edenberg, 2007).…”

Section: Revisão De Literaturaunclassified

Repercussões minerais ósseas no alcoolismo crônico associado à deficiência hormonal em ratos

Lodi¹

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Effects of Antioxidants in Fermented Beverages in Tissue Transcriptomics: Effect of Beer Intake on Myocardial Tissue after Oxidative Injury

et al. 2023

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Fermented beverages, such as wine and beer, are rich in polyphenols that have been shown to have protective effects against oxidative stress. Oxidative stress plays a central role in the pathogenesis and progression of cardiovascular disease. However, the potential benefits of fermented beverages on cardiovascular health need to be fully investigated at a molecular level. In this study, we aimed at analyzing the effects of beer consumption in modulating the transcriptomic response of the heart to an oxidative stress challenge induced by myocardial ischemia (MI) in the presence of hypercholesterolemia in a pre-clinical swine model. Previous studies have shown that the same intervention induces organ protective benefits. We report a dose-dependent up-regulation of electron transport chain members and the down-regulation of spliceosome-associated genes linked to beer consumption. Additionally, low-dose beer consumption resulted in a down-regulation of genes associated with the immune response, that was not shown for moderate-dose beer consumption. These findings, observed in animals having demonstrated beneficial effects at the organ-level, indicate that the antioxidants in beer differentially affect the myocardial transcriptome in a dose-dependent manner.

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Biodistribution of Radiolabeled Ethanol in Rodents

Abstract: ABSTRACT:The biodistribution of [1- 14

Cited by 4 publications

References 27 publications

Metabolic disposition of the anti-cancer agent [¹⁴C]laromustine in male rats

Metabolic disposition of the anti-cancer agent [¹⁴C]laromustine in male rats

Repercussões minerais ósseas no alcoolismo crônico associado à deficiência hormonal em ratos

Effects of Antioxidants in Fermented Beverages in Tissue Transcriptomics: Effect of Beer Intake on Myocardial Tissue after Oxidative Injury

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Biodistribution of Radiolabeled Ethanol in Rodents

Abstract: ABSTRACT:The biodistribution of [1- 14

Cited by 4 publications

References 27 publications

Metabolic disposition of the anti-cancer agent [14C]laromustine in male rats

Metabolic disposition of the anti-cancer agent [14C]laromustine in male rats

Repercussões minerais ósseas no alcoolismo crônico associado à deficiência hormonal em ratos

Effects of Antioxidants in Fermented Beverages in Tissue Transcriptomics: Effect of Beer Intake on Myocardial Tissue after Oxidative Injury

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Metabolic disposition of the anti-cancer agent [¹⁴C]laromustine in male rats

Metabolic disposition of the anti-cancer agent [¹⁴C]laromustine in male rats