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• W2097134501 abstract "Mass balance and metabolism studies using radiolabeled substances are well recognized as an important part of the drug development process. In this study, we directly assessed the use of fluorine nuclear magnetic resonance (¹⁹F NMR) to achieve quantitative mass balance, metabolism, and distribution information for fluorinated compounds, without the need for radiolabeled synthesis or study. As a test case, the disposition of pefloxacin, a fluoroquinolone antibiotic, was evaluated in rats using quantitative ¹⁹F NMR in parallel with a radiolabeled study. Urine, bile, and feces samples were collected over specific periods after oral administration of either 25 mg/kg [¹⁴C]pefloxacin or 25 mg/kg pefloxacin and were subsequently profiled by radioactivity or ¹⁹F NMR, respectively. The percentage of dose excreted in each matrix was comparable between the two methods, with the total dose recovered by radioactivity and ¹⁹F NMR determined to be 86.8% and 81.8%, respectively. In addition, plasma samples were collected to determine the exposure of pefloxacin and its circulating metabolites. The plasma exposure of pefloxacin determined by ¹⁹F NMR was within 5% to that calculated by a validated liquid chromatography-tandem mass spectrometry bioanalytical method. By both methods, pefloxacin was identified as the major circulating entity, with pefloxacin glucuronide as the major circulating metabolite. Quantitative analysis of metabolites in excreta was generally comparable between the two methods. In selected tissues, both methods indicated that the parent drug accounted for most of the drug-related material. In summary, we have demonstrated that ¹⁹F NMR can be used as an alternative method to conventional radiolabeled studies for compounds containing fluorine without the need for radiolabeled synthesis/study." @default.
• W2097134501 created "2016-06-24" @default.
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• W2097134501 date "1869-01-23" @default.
• W2097134501 modified "2023-09-27" @default.
• W2097134501 title "On the Plugging of Minute Vessels in the Grey Matter of the Brain, as a Cause of the Delirium and Stupor in Severe Febrile Diseases; and on Other Symptoms of the 'Typhoid State'" @default.
• W2097134501 doi "https://doi.org/10.1136/bmj.1.421.66" @default.
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