van Maanen M J, Huitema A D, Rodenhuis S, Beijnen J H
Division of Drug Toxicology, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
Anticancer Drugs. 2001 Jul;12(6):519-24. doi: 10.1097/00001813-200107000-00005.
The urinary excretion of N,N',N"-triethylenethiophosphoramide (thioTEPA), and its metabolites N,N',N"-triethylenephosphoramide (TEPA), N,N'-diethylene,N"-2-chloroethylphosphoramide (monochloroTEPA) and thioTEPA--mercapturate was determined in patients receiving thioTEPA as part of a high-dose combination chemotherapy regimen with cyclophosphamide and carboplatin. The thioTEPA dose was 40 or 60 mg/m(2) in short infusions, twice daily, during 4 days. Urine samples were collected after each voiding on each day of drug administration until 24--48 h after the last thioTEPA infusion. ThioTEPA, TEPA and monochloroTEPA concentrations were determined with gas chromatography and thioTEPA--mercapturate with liquid chromatography--mass spectrometry with direct sample injection. ThioTEPA was present in urine 30 min after infusion and was still excreted 18 h after the last infusion. All metabolites were detected in urine 1 h after infusion. Patients with a creatinine clearance above 140 ml/minl showed higher excretion of TEPA than patients with a creatinine clearance below 140 ml/min (12.8 versus 4.9%, p=0.01). The excretion of monochloroTEPA relative to the excreted amount of TEPA increased at lower pH values of the urine. The excretion of thioTEPA--mercapturate relative to the dose was higher in patients treated with 60 mg/m(2). Excretion of thioTEPA and monochloroTEPA both accounted for only 0.5% of the dose, while TEPA and thioTEPA--mercapturate both accounted for 11.1%.
在接受硫替派作为环磷酰胺和卡铂高剂量联合化疗方案一部分的患者中，测定了N,N',N''-三乙烯硫代磷酰胺（硫替派）及其代谢产物N,N',N''-三乙烯磷酰胺（替派）、N,N'-二乙烯基,N''-2-氯乙基磷酰胺（单氯替派）和硫替派-巯基尿酸盐的尿排泄情况。硫替派剂量为40或60mg/m²，短时间输注，每日两次，共4天。在给药的每一天每次排尿后收集尿液样本，直至最后一次硫替派输注后24 - 48小时。用气相色谱法测定硫替派、替派和单氯替派的浓度，用直接进样的液相色谱-质谱法测定硫替派-巯基尿酸盐的浓度。输注后30分钟尿液中出现硫替派，最后一次输注后18小时仍有排泄。输注后1小时在尿液中检测到所有代谢产物。肌酐清除率高于140ml/min的患者比肌酐清除率低于140ml/min的患者显示出更高的替派排泄率（12.8%对4.9%，p = 0.01）。尿液pH值较低时，单氯替派相对于替派排泄量的排泄率增加。接受60mg/m²治疗的患者中，硫替派-巯基尿酸盐相对于剂量的排泄率更高。硫替派和单氯替派的排泄量均仅占剂量的0.5%，而替派和硫替派-巯基尿酸盐均占11.1%。
