Workman P, Newman H F, Bleehen N M, Ward R, Smithen C E
MRC Clinical Oncology and Radiotherapeutics Unit, Cambridge, UK.
Cancer Chemother Pharmacol. 1991;28(2):118-22. doi: 10.1007/BF00689700.
During a clinical toxicity study it was possible to obtain urine samples from six patients receiving either the R-(-)- or S-(+)-stereoenantiomeric forms of the developmental 2-nitroimidazole radiosensitizer Ro 03-8799 (pimonidazole). Paired plasma samples were also obtained from four patients. The pharmacokinetic data were compared with those for the racemic mixture in the same individuals. The results revealed no major differences in the plasma pharmacokinetics, urinary clearance or N-oxidation of the individual enantiomers as compared with the racemic mixture. A similar lack of stereoselectivity with respect to the acute dose-limiting CNS toxicity syndrome suggests that this may not involve a specific CNS receptor interaction.
在一项临床毒性研究中，有可能从六名接受发育型2-硝基咪唑放射增敏剂Ro 03-8799（匹莫硝唑）的R-(-)-或S-(+)-立体对映体形式的患者身上获取尿液样本。还从四名患者身上获取了配对的血浆样本。将药代动力学数据与同一患者的消旋混合物的数据进行了比较。结果显示，与消旋混合物相比，各对映体在血浆药代动力学、尿清除率或N-氧化方面没有重大差异。关于急性剂量限制性中枢神经系统毒性综合征缺乏类似的立体选择性，这表明这可能不涉及特定的中枢神经系统受体相互作用。
