Dodion P, Egorin M J, Engisch K L, Bachur N R
Cancer Res. 1985 Nov;45(11 Pt 1):5352-7.
We have investigated the metabolism and disposition, in rabbits, of menogaril (7-OMEN), a new anthracycline antibiotic recently introduced into clinical trials. 7-OMEN was administered by rapid i.v. injection at a dosage of 2.5 mg/kg. 7-OMEN and metabolites were assayed by high performance liquid chromatography. Plasma concentrations of 7-OMEN declined in biexponential fashion with a terminal half-life of 2.7 h. The area under the plasma concentration versus time curve was 1.3 microM X h. The systemic clearance of 7-OMEN was 57.6 ml/min/kg. No metabolite of 7-OMEN was detected in plasma. At 8 h after treatment, the cumulative urinary and biliary excretions of 7-OMEN equivalents amounted to 1.3 and 3.4% of the total administered dose, respectively. 7-OMEN was the predominant fluorescent compound in urine, but four metabolites were also seen. In bile, 7-OMEN represented only 9.6% of the cumulative excretion and six metabolites were observed. Among the organs, lungs contained the highest concentrations of parent drug. Substantial concentrations of metabolites were observed in the kidneys, liver, duodenum, and small intestine. Three of the observed metabolites of 7-OMEN have been tentatively identified as N-demethylmenogaril, 7-deoxynogarol, and N-demethyl-7-deoxynogarol.
我们研究了美诺加（7-OMEN）在兔体内的代谢和处置情况，美诺加是一种最近进入临床试验的新型蒽环类抗生素。以2.5mg/kg的剂量通过快速静脉注射给予7-OMEN。采用高效液相色谱法测定7-OMEN及其代谢产物。7-OMEN的血浆浓度呈双指数下降，终末半衰期为2.7小时。血浆浓度-时间曲线下面积为1.3μM×h。7-OMEN的全身清除率为57.6ml/min/kg。血浆中未检测到7-OMEN的代谢产物。治疗后8小时，7-OMEN等效物的累积尿排泄和胆汁排泄分别占总给药剂量的1.3%和3.4%。7-OMEN是尿液中主要的荧光化合物，但也可见四种代谢产物。在胆汁中，7-OMEN仅占累积排泄量的9.6%，观察到六种代谢产物。在各器官中，肺中母体药物浓度最高。在肾脏、肝脏、十二指肠和小肠中观察到大量代谢产物。7-OMEN观察到的三种代谢产物已初步鉴定为N-去甲基美诺加、7-脱氧诺加罗和N-去甲基-7-脱氧诺加罗。
