Schierl R, Rohrer B, Hohnloser J
Institut und Poliklinik für Arbeitsmedizin, Ludwig-Maximilians-Universit at M unchen, Germany.
Cancer Chemother Pharmacol. 1995;36(1):75-8. doi: 10.1007/BF00685736.
The purpose of this study was to determine long-term renal platinum excretion after chemotherapy with cisplatin. We examined urinary platinum concentrations in 23 men at 150-3022 days after anticancer treatment for testicular neoplasm. Spot urine samples were analyzed by voltammetry. This new, subtle method with a detection limit of 2 pg platinum allows determination of even the natural background level. Urinary platinum concentrations in our patients ranged between 0.74 and 77.24 micrograms/g creatinine, depending on the total delivered dose and follow-up period. Regression analysis of the data showed two phases of long-term renal platinum excretion, one occurring at between 150 and 900 days of follow-up and the other with an onset at 900 days after cisplatin administration (r1(2) = 0.82, r2(2) = 0.88). Two biological half-lives of 160 and 720 days were calculated. Our results show that urinary platinum concentrations determined at 8 years after cisplatin therapy are 40 times higher than the background level (up to 0.02 micrograms/g creatinine). Our findings on the long-term pharmacokinetics of this anticancer agent may facilitate further studies on sites of platinum storage in the human body as well as clinical studies on the late adverse effects of cisplatin.
本研究的目的是确定顺铂化疗后肾脏铂的长期排泄情况。我们检测了23名男性在接受睾丸肿瘤抗癌治疗后150 - 3022天的尿铂浓度。随机尿样采用伏安法进行分析。这种新的、灵敏的方法检测限为2皮克铂,甚至可以测定自然背景水平。根据总给药剂量和随访时间,我们患者的尿铂浓度在0.74至77.24微克/克肌酐之间。对数据的回归分析显示肾脏铂长期排泄有两个阶段,一个阶段发生在随访的150至900天之间,另一个阶段在顺铂给药后900天开始(r1(2) = 0.82,r2(2) = 0.88)。计算出两个生物半衰期分别为160天和720天。我们的结果表明,顺铂治疗8年后测定的尿铂浓度比背景水平高40倍(高达0.02微克/克肌酐)。我们关于这种抗癌药物长期药代动力学的研究结果可能有助于进一步研究铂在人体中的储存部位以及顺铂晚期不良反应的临床研究。