Kangarloo Shahbal B, Gangopadhyay Suman B, Syme Rachel M, Wolff Johannes E A, Glück Stefan
Department of Oncology, Faculty of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 29th Street NW, Calgary, Alberta T2N 4N2 Canada.
Med Oncol. 2004;21(1):9-20. doi: 10.1385/MO:21:1:09.
Mesna, a reactive thiol, often encounters cisplatin and carboplatin in combination protocols involving oxazaphosphorines and platinum drugs. This co-administration might be unfavorable based on the inactivation of platinum drugs by thiol groups in vitro. We investigated whether mesna influences the pharmacokinetics of platinum drugs when co-administered with cisplatin or carboplatin. The pharmacokinetics of platinum drugs were investigated in 18 pediatric patients receiving either cisplatin or carboplatin in a combination with or without mesna. In cisplatin patients, a decrease in the distribution clearance of total platinum was observed when mesna was co-administered (CLd, 2.2 +/- 0.1 mL/min.kg; n = 3), compared to cisplatin without mesna (CLd, 4.8 +/- 1.5 mL/min.kg; n = 5) (p = 0.029, t-test). This might have been caused by an influence of mesna in slowing down the protein binding of cisplatin since a trend (p = 0.057) in prolonged distribution half-life of total platinum was also observed when mesna was present (t(1/2a) 65 +/- 21 min; n = 3) compared to cisplatin without mesna (t(1/2a), 32 +/- 18 min; n = 5). However, the impact of these changes on the area under the concentration time curve (AUC), total clearance (CLt), and volume of distribution (V) for total platinum and ultrafilterable platinum species was hardly noticeable. In carboplatin patients, when mesna was co-administered: AUC (2.5 +/- 0.4 mg.min/mL.400 mg/m2; n = 5) CLt, (6.8 +/- 5.1 mL/min.kg; n = 6), and V (0.7 +/- 0.4 L/kg; n = 6) for ultrafilterable platinum species were not significantly different from when carboplatin were administered without mesna: AUC (2.3 +/- 1.3 mg.min/mL.400 mg/m2; n = 4), CLt (5.8 +/- 4.6 mL/min.kg; n = 5), and V (1.1 +/- 1.1 L/kg; n = 5). Hence, mesna does not significantly influence the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.
美司钠是一种活性硫醇，在涉及氧氮磷杂环化合物和铂类药物的联合用药方案中常与顺铂和卡铂同时使用。基于体外硫醇基团使铂类药物失活，这种联合用药可能不利。我们研究了美司钠与顺铂或卡铂合用时是否会影响铂类药物的药代动力学。在18例接受顺铂或卡铂联合或不联合美司钠治疗的儿科患者中研究了铂类药物的药代动力学。在顺铂治疗的患者中，与未使用美司钠的顺铂治疗组相比（分布清除率CLd，4.8±1.5 mL/min·kg；n = 5），当联合使用美司钠时观察到总铂的分布清除率降低（CLd，2.2±0.1 mL/min·kg；n = 3）（p = 0.029，t检验）。这可能是由于美司钠影响了顺铂与蛋白质的结合，导致其速度减慢，因为当使用美司钠时也观察到总铂的分布半衰期有延长的趋势（p = 0.057）（t(1/2a) 65±21分钟；n = 3），而未使用美司钠的顺铂治疗组（t(1/2a)，32±18分钟；n = 5）。然而，这些变化对总铂和可超滤铂物种的浓度时间曲线下面积（AUC）、总清除率（CLt）和分布容积（V）的影响几乎不明显。在卡铂治疗的患者中，当联合使用美司钠时：可超滤铂物种的AUC（2.5±0.4 mg·min/mL·400 mg/m2；n = 5）、CLt（6.8±5.1 mL/min·kg；n = 6）和V（0.7±0.4 L/kg；n = 6）与未使用美司钠的卡铂治疗组相比无显著差异：AUC（2.3±1.3 mg·min/mL·400 mg/m2；n = 4）、CLt（5.8±4.6 mL/min·kg；n = 5）和V（1.1±1.1 L/kg；n = 5）。因此，美司钠对儿科癌症患者顺铂和卡铂的药代动力学没有显著影响。
