Newman H F, Dunphy E P, Bleehen N M, Dische S, Saunders M I, Des Rochers C, Workman P, Lenox-Smith I, Smithen C E
Br J Radiol. 1986 Oct;59(706):997-9. doi: 10.1259/0007-1285-59-706-997.
The maximum single dose of the 2-nitroimidazole hypoxic cell radiosensitiser Ro 03-8799 is limited to 1 g/m2 by the occurrence of a well characterised acute syndrome of sweating, nausea and mental changes. In an attempt to increase the tolerable dose, the clinical toxicity of the racemic mixture was compared with that of the R- and S-enantiomers of Ro 03-8799. Twelve patients received escalating alternate doses of racemic mixture and R- or S-enantiomer, the dose levels being 0.25 g/m2, 0.5 g/m2, 0.75 g/m2 and 1.0 g/m2. Careful monitoring of the acute syndrome failed to demonstrate any consistent differences between racemic mixture and either enantiomer. This would suggest that the toxicity is not mediated via any specific central nervous system receptor. It is concluded that separation of Ro 03-8799 into its enantiomers will not enable a clinically useful increase in dosage.
2-硝基咪唑类乏氧细胞放射增敏剂Ro 03-8799的最大单次剂量因出现特征明显的急性综合征（出汗、恶心和精神变化）而限制在1 g/m²。为了提高可耐受剂量，将外消旋混合物的临床毒性与Ro 03-8799的R-和S-对映体的毒性进行了比较。12名患者接受了递增的外消旋混合物和R-或S-对映体交替剂量，剂量水平分别为0.25 g/m²、0.5 g/m²、0.75 g/m²和1.0 g/m²。对急性综合征的仔细监测未能显示出外消旋混合物与任何一种对映体之间存在任何一致的差异。这表明毒性不是通过任何特定的中枢神经系统受体介导的。结论是，将Ro 03-8799拆分成其对映体并不能在临床上有效增加剂量。
