Raoul J L, Heresbach D, Bretagne J F, Ferrer D B, Duvauferrier R, Bourguet P, Messner M, Gosselin M
Department of Hepatogastroenterology, Hôpital Pontchaillou, Rennes, France.
Cancer. 1992 Aug 1;70(3):585-90. doi: 10.1002/1097-0142(19920801)70:3<585::aid-cncr2820700308>3.0.co;2-#.
This study evaluated the effects of an association of ethiodized oil (Lipiodol Ultra Fluide, Laboratoires Guerbet, Aulnay-sous-Bois, France), with or without gelatin sponge, with doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) on the biodistribution and kinetics of doxorubicin during intraarterial injection.
Eighteen patients with hepatocellular carcinoma on cirrhotic liver received a therapeutic injection into the hepatic artery of 50 mg of doxorubicin alone (Group 1; n = 4), or emulsified in 10 ml of ethiodized oil and 2.5 ml of ioxaglate (Hexabrix, Laboratoires Guerbet) with (Group 2; n = 7) or without (Group 3; n = 7) gelatin sponge embolization. Before treatment, the absence of intrahepatic shunts was verified by an injection of technetium-labeled albumin macroaggregates. The biodistribution of doxorubicin was studied on two fronts: (1) pharmacokinetic--by measurement of the doxorubicin blood level during the 48 hours after injection; and (2) scintigraphic (2 mg of doxorubicin were labeled with 2 mCi of iodine 131)--by examination of the scintigrams and calculation of the following parameters: tumours liver/nontumorous liver binding ratio (T/NT ratio), liver/liver+lungs+abdomen binding ratio, and doxorubicin half-life in tumorous tissue.
Pharmacokinetics results showed the following: the peak plasma concentration was significantly higher in Group 1 as compared with Groups 2 or 3 (Group 1: 2.1 +/- 0.9 mg/ml; Group 2: 0.9 +/- 0.3 mg/ml; Group 3: 0.5 +/- 0.2 mg/ml); the area under curve calculated from time zero to 1 hour was lower in Groups 2 and 3 compared with Group 1. Examination of the scintigrams showed the following: diffuse activity throughout the organism (Group 1), diffuse activity with strong hepatic and tumorous binding (Group 2), and mostly hepatic and tumoral binding (Group 3). The liver/liver+lungs+abdomen binding ratio was 28% +/- 1% in Group 1, 36% +/- 5% in Group 2, and 63% +/- 7% in Group 3. The T/NT ratios were 1.0 +/- 0 (Group 1), 1.5 +/- 0.1 (Group 2), and 4.7 +/- 0.5 (Group 3). The doxorubicin half-lives in tumourous tissue were 0.7 +/- 0.1 days (Group 1), 1.8 +/- 0.2 days (Group 2), and 2.6 days (n = 1; Group 3).
This study shows (1) that the association of ethiodized oil with doxorubicin lowers the peak concentration of doxorubicin and increases the intratumoral concentration and half-life of doxorubicin, and (2) that these kinetic ameliorations are even more pronounced after embolization. Therefore, from a kinetic standpoint, the doxorubicin-ethiodized oil-gelatin sponge association is the best.
本研究评估了乙碘油（超液态碘化油，法国吉贝尔实验室，奥奈苏布瓦）联合或不联合明胶海绵与阿霉素（阿霉素，阿德里亚实验室，俄亥俄州哥伦布市）对动脉内注射阿霉素期间其生物分布和动力学的影响。
18例肝硬化肝的肝细胞癌患者接受了肝动脉内治疗性注射，分别为单独注射50mg阿霉素（第1组；n = 4），或阿霉素乳化于10ml乙碘油和2.5ml碘克沙醇（六溴化泛影葡胺，法国吉贝尔实验室）中并联合（第2组；n = 7）或不联合（第3组；n = 7）明胶海绵栓塞。治疗前，通过注射锝标记的白蛋白大颗粒来验证肝内分流的不存在。阿霉素的生物分布从两个方面进行研究：（1）药代动力学——通过测量注射后48小时内阿霉素的血药浓度；（2）闪烁扫描法（2mg阿霉素用2mCi碘131标记）——通过检查闪烁扫描图并计算以下参数：肿瘤肝/非肿瘤肝结合率（T/NT比值）、肝/肝 + 肺 + 腹部结合率以及阿霉素在肿瘤组织中的半衰期。
药代动力学结果显示如下：与第2组或第3组相比，第1组的血浆峰浓度显著更高（第1组：2.1±0.9mg/ml；第2组：0.9±0.3mg/ml；第3组：0.5±0.2mg/ml）；从时间零点到1小时计算的曲线下面积，第2组和第3组低于第1组。闪烁扫描图检查显示如下：全身弥漫性活性（第1组），弥漫性活性伴肝脏和肿瘤强烈结合（第2组），以及主要为肝脏和肿瘤结合（第3组）。肝/肝 + 肺 + 腹部结合率在第1组为28%±1%，第2组为36%±5%，第3组为63%±
