Department of Interventional Radiology, Institute Gustave Roussy, Villejuif, 94805, France.
Cardiovasc Intervent Radiol. 2012 Dec;35(6):1448-59. doi: 10.1007/s00270-012-0343-y. Epub 2012 Feb 23.
The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform.
Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.
Twelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03).
Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.
本研究旨在研究静脉内、肝内动脉内或载入给药平台的伊立替康的药代动力学。
54 只新西兰白兔患有 VX2 肝肿瘤，分为 3 组，每组 17 只，分别接受静脉内（IV）途径、肝内动脉（IA）途径或载入载药微球（DEBIRI）的伊立替康。动物在 1、6 和 24 小时时处死。在不同时间点测量血清、肿瘤和正常肝脏中的伊立替康和 SN-38 浓度。
IV 和 IA 分别注射 12 毫克伊立替康，而载入 DEBIRI 的则为 6-16.5 毫克。IV 时，血清伊立替康的标准化峰值达到 333ng/ml（范围 198.8-502.5），IA 时达到 327.1ng/ml（范围 277.1-495.6），而 DEBIRI 时达到 189.7ng/ml（范围 111.1-261.9）（P<0.001）。血清伊立替康浓度 10-60 分钟的 AUC 值在 DEBIRI 时显著降低（P=0.0009）。IV、IA 和 DEBIRI 的肿瘤伊立替康水平（以每 200mg 组织中的 ng 为单位，括号内为范围）分别为 1 小时时 23.6（0.3-24.9）、36.5（7.7-1914.1）和 20.2（2.9-319）；6 小时时为 4.2（1-27.9）、99.3（46.6-159.5）和 42.1（11.3-189）；24 小时时为 2.7（2.5-6.9）、18.3（1.5-369.1）和 174.4（3.4-5147.3）（P=0.02）。24 小时时，肿瘤坏死率分别为 IV（10-30）、IA（60%（40-91.25）和 DEBIRI（95%（76.25-95）（P=0.03）。
与 IV 或 IA 相比，DEBIRI 诱导早期血清伊立替康水平较低，肿瘤内水平较高且持续时间较长，24 小时时肿瘤坏死率更高。需要进一步评估 DEBIRI 的临床获益。
