接受异环磷酰胺治疗的人体会排出硫代二甘醇酸，它会抑制大鼠的线粒体功能。
Thiodiglycolic acid is excreted by humans receiving ifosfamide and inhibits mitochondrial function in rats.
作者信息
Visarius T M, Bähler H, Küpfer A, Cerny T, Lauterburg B H
机构信息
Clinical Pharmacology, University of Berne, Berne, Switzerland.
出版信息
Drug Metab Dispos. 1998 Mar;26(3):193-6.
Thiodiglycolic acid has been identified as a major metabolite of the anticancer drug ifosfamide in humans. Patients treated with 12-16 g ifosfamide/m2.day excreted thiodiglycolic acid ranging from 0.10 +/- 0.02 mmol on the first day of therapy, to a maximum of 3.27 +/- 0.15 mmol on the fourth day of ifosfamide infusion. This amounted to 5.4 +/- 0.2% of the administered dose of ifosfamide appearing as thiodiglycolic acid in urine during a 5 days' continuous ifosfamide infusion. Thiodiglycolic acid (50mg/kg) administered to rats inhibited the carnitine-dependent oxidation of [1-14C]palmitic acid by 55%, but affected neither the oxidation of [1-14C]octanoic acid, which is carnitine-independent, nor the oxidation of [1, 4-14C]succinic acid, a marker of Kreb's cycle activity. Additionally, thiodiglycolic acid (30 microM) inhibited oxidation of palmitic acid but not palmitoyl-L-carnitine in isolated rat liver mitochondria, indicating that it either sequesters carnitine or inhibits carnitine palmitoyltransferase I. This study elucidates a specific mitochondrial dysfunction induced by thiodiglycolic acid which may contribute to the adverse effects associated with ifosfamide chemotherapy.
硫代二乙醇酸已被确认为抗癌药物异环磷酰胺在人体内的主要代谢产物。接受12 - 16 g异环磷酰胺/平方米·天治疗的患者，在治疗第一天排出的硫代二乙醇酸为0.10±0.02 mmol，在异环磷酰胺输注第四天达到最高值3.27±0.15 mmol。在连续5天输注异环磷酰胺期间，尿液中以硫代二乙醇酸形式出现的异环磷酰胺给药剂量占5.4±0.2%。给大鼠注射硫代二乙醇酸（50mg/kg）可使[1-14C]棕榈酸的肉碱依赖性氧化作用降低55%，但对不依赖肉碱的[1-14C]辛酸氧化作用以及作为三羧酸循环活性标志物的[1, 4-14C]琥珀酸氧化作用均无影响。此外，硫代二乙醇酸（30 microM）在离体大鼠肝线粒体中抑制棕榈酸的氧化，但不抑制棕榈酰-L-肉碱的氧化，这表明它要么螯合肉碱，要么抑制肉碱棕榈酰转移酶I。本研究阐明了硫代二乙醇酸诱导的一种特定线粒体功能障碍，这可能是异环磷酰胺化疗相关不良反应的原因。
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