Gamelin E, Allain P, Maillart P, Turcant A, Delva R, Lortholary A, Larra F
Service d'Oncologie Médicale, Centre Paul Papin, Angers, France.
Cancer Chemother Pharmacol. 1995;37(1-2):97-102. doi: 10.1007/BF00685635.
The platinum concentration in plasma was studied in 19 patients treated by 3 or 4 successive courses of chemotherapy including cisplatin for head and neck cancers.
Cisplatin was given i.v. daily at 25 mg/m2 by 1-h infusions for 4 days every 3 weeks. Total and ultrafiltrable platinum were measured in plasma using an inductively coupled plasma mass spectrometry (ICPMS) technique.
A progressive accumulation of total platinum in plasma was observed with consecutive infusions. The mean (+/- SD) total plasma platinum level detected at the end of cisplatin infusion was 1134 +/- 234, 1407 +/- 268, and 1618 +/- 282 micrograms/l at the end of the first, second, and third courses, respectively. The minimal platinum concentration measured before the second and third courses also increased to 221 +/- 59 and 309 +/- 76 micrograms/l, respectively. The steady state was not reached before the third course. However, differences in the evolution of platinum plasma levels were found among the 19 patients. In 14 patients the pharmacokinetics of platinum was characterized by low initial levels, a progressive accumulation, and a long terminal half-life with a very late steady state. In 5 patients, the pharmacokinetic behavior of platinum was different: platinum levels were directly high, without progressive accumulation, the steady state being reached as early as the first course. Significant levels of ultrafiltrable platinum were found throughout the treatment, even during the intervals between courses with this very sensitive analytical method. A close equilibrium between ultrafiltrable and total platinum (ratio, 6%) persisted for as long as 3 weeks after cisplatin administration.
These results underline the importance of individual differences in platinum metabolism. The relationship between total and ultrafiltrable platinum are discussed.
对19例接受3或4个连续疗程含顺铂化疗方案治疗的头颈癌患者的血浆铂浓度进行研究。
顺铂以25mg/m²的剂量静脉滴注，每日1次，每次输注1小时，每3周进行4天。使用电感耦合等离子体质谱（ICPMS）技术测定血浆中的总铂和可超滤铂。
连续输注后观察到血浆中总铂的逐渐积累。在顺铂输注结束时，第一、第二和第三疗程结束时检测到的平均（±标准差）血浆总铂水平分别为1134±234、1407±268和1618±282μg/L。在第二和第三疗程前测得的最低铂浓度也分别增加到221±59和309±76μg/L。在第三疗程之前未达到稳态。然而，19例患者中发现铂血浆水平的变化存在差异。在14例患者中，铂的药代动力学特征为初始水平低、逐渐积累、终末半衰期长且稳态出现很晚。在5例患者中，铂的药代动力学行为不同：铂水平直接很高，无逐渐积累，早在第一疗程就达到了稳态。即使在疗程间隔期间，使用这种非常灵敏的分析方法也能在整个治疗过程中检测到显著水平的可超滤铂。顺铂给药后长达3周，可超滤铂与总铂之间保持密切平衡（比率为6%）。
这些结果强调了铂代谢个体差异的重要性。讨论了总铂和可超滤铂之间的关系。
