Hutson P R, Tutsch K D, Rago R, Arzoomanian R, Alberti D, Pomplun M, Church D, Marnocha R, Cheng A L, Kehrli N, Wilding G
University of Wisconsin Comprehensive Cancer Center, Madison 53792, USA.
Clin Cancer Res. 1998 Jun;4(6):1429-36.
Suramin was administered to 49 patients in a Phase I cancer trial with real-time pharmacokinetic monitoring and dose individualization to achieve targeted mean plasma concentrations of 210 and 155 mg/liter during the 7-day period between days 15 and 22. Pharmacokinetic sampling after doses on days 1, 3, 5, and 8 was used to modify weekly suramin doses, beginning on day 15, in an attempt to achieve specific averaged plasma concentrations of 210 and 155 mg/liter. A 200-mg test dose was not effective in prospectively determining individual pharmacokinetic parameters and dosage requirements. Patients with peak plasma suramin concentrations in excess of 350 mg/liter may be more likely to experience neurotoxicity (P = 0.06), but there was no statistically significant effect of peak suramin concentration or of cumulative dose. Biopsy and autopsy tissue samples demonstrated low penetration of suramin into brain tissue and muscle but good penetration into prostate and other visceral organs. Prospective use of surrogate substrates for CYP1A2, CYP3A3/4, and CYP2D6 showed no consistent effect of suramin on these enzymes. Although a correlation between creatinine clearance and suramin renal clearance was found (r2 = 0.38; P < 0.00005), there was no correlation between creatinine clearance and total suramin clearance (P = 0.21). No suramin dose modification for renal or hepatic dysfunction can be supported at this time. Three of four ovarian cancer patients demonstrated a drop in CA-125 serum concentrations during suramin treatment.
在一项I期癌症试验中，对49名患者给予苏拉明，并进行实时药代动力学监测和剂量个体化，以在第15天至22天的7天期间实现目标平均血浆浓度210和155毫克/升。在第1、3、5和8天给药后进行药代动力学采样，从第15天开始用于调整每周苏拉明剂量，试图达到210和155毫克/升的特定平均血浆浓度。200毫克的试验剂量在前瞻性确定个体药代动力学参数和剂量需求方面无效。血浆苏拉明峰值浓度超过350毫克/升的患者可能更易出现神经毒性（P = 0.06），但苏拉明峰值浓度或累积剂量无统计学显著影响。活检和尸检组织样本显示苏拉明在脑组织和肌肉中的渗透较低，但在前列腺和其他内脏器官中的渗透良好。对CYP1A2、CYP3A3/4和CYP2D6的替代底物进行前瞻性研究表明，苏拉明对这些酶无一致影响。尽管发现肌酐清除率与苏拉明肾清除率之间存在相关性（r2 = 0.38；P < 0.00005），但肌酐清除率与苏拉明总清除率之间无相关性（P = 0.21）。目前无法支持因肾功能或肝功能障碍而对苏拉明剂量进行调整。四名卵巢癌患者中有三名在苏拉明治疗期间血清CA - 125浓度下降。
