Division of Medical Oncology, Department of Medicine, Columbia University Medical Center, New York, NY, USA.
Ann Surg Oncol. 2013 Apr;20(4):1101-4. doi: 10.1245/s10434-012-2790-8. Epub 2013 Mar 2.
Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia.
We collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m(2) oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance.
Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels.
Higher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA.
高热术中腹腔内化疗（HIPEC）用于治疗腹膜表面扩散性恶性肿瘤，以最大限度地提高局部药物浓度，同时最大限度地减少全身效应。HIPEC 的药代动力学优势定义为药物浓度的腹腔内与血管内比值。我们假设体表面积（BSA）与 HIPEC 的药代动力学优势相关。由于奥沙利铂在 5%葡萄糖中给药，我们假设 BSA 与血糖相关。
我们从 10 名接受 HIPEC 治疗的患者中收集了血液和腹腔灌流液样本，BSA 基础剂量为 250mg/m²奥沙利铂，并通过电感耦合等离子体质谱法测量了药物浓度。我们在术后 24 小时监测血糖。通过梯形法则计算浓度时间曲线下面积（AUC）。药代动力学优势通过（腹腔液 AUC/血浆 AUC）计算。我们使用线性回归来测试统计学意义。
较高的 BSA 与较低的血浆奥沙利铂 AUC（p=0.0075）和 HIPEC 期间 60 分钟的更大药代动力学优势（p=0.0198）相关。BSA 与血糖 AUC 或峰值血糖水平之间未发现统计学上显著的关系。
较高的 BSA 与 HIPEC 中较低的血浆药物水平和更大的药代动力学优势相关，可能是由于循环血量增加而平衡时间不足。奥沙利铂 HIPEC 后的血糖水平与 BSA 不明确相关。
