Malet-Martino M C, Martino R
Laboratoire des IMRCP, URA CNRS 470, Université Paul Sabatier, Toulouse, France.
Biochimie. 1992 Sep-Oct;74(9-10):785-800. doi: 10.1016/0300-9084(92)90061-i.
Studies on the metabolism and disposition of drugs using nuclear magnetic resonance spectroscopy (MRS) as the analytical technique are reviewed. An overview of the main studies classed in terms of the observed magnetic nucleus (1H, 2H, 7Li, 13C, 19F, 31P, 77Se) is followed by some typical examples of the way in which 19F and 31P MRS can be profitably employed to gain more understanding about the metabolism and disposition of the anticancer fluoropyrimidines (5-fluorouracil (FU) and its prodrugs) and ifosfamide (IF). The results of three recent studies carried out in our laboratory are developed. They concern the direct quantitative monitoring of the hepatic metabolism of FU in the isolated perfused mouse liver, the elucidation of the origin of the cardiotoxicity of FU and the metabolism of IF from an analysis of biofluids of patients. Finally, the advantages and limitations of MRS for investigations on drug metabolism are discussed.
综述了利用核磁共振波谱法(MRS)作为分析技术对药物代谢和处置的研究。首先按观察到的磁核(1H、2H、7Li、13C、19F、31P、77Se)对主要研究进行了概述,随后给出了一些典型示例,说明如何有效地利用19F和31P MRS来更深入了解抗癌氟嘧啶(5-氟尿嘧啶(FU)及其前药)和异环磷酰胺(IF)的代谢和处置。阐述了我们实验室最近开展的三项研究结果。这些研究涉及在离体灌注小鼠肝脏中对FU肝代谢的直接定量监测、FU心脏毒性起源的阐明以及通过对患者生物流体的分析研究IF的代谢。最后,讨论了MRS在药物代谢研究中的优点和局限性。