Abramson D H, Frank C M, Chantada G L, de Totah A B, de Pifano I T, Ramírez G T, Gomez R T, Fandino A T, Tran H T, Madden T J, Dunkel I J
New York Hopsital-Cornell University Medical Center, New York, NY, USA.
Ophthalmic Genet. 1999 Mar;20(1):31-6. doi: 10.1076/opge.20.1.31.2302.
Previous studies of the penetration of carboplatin into the vitreous have depended on unaffected animals or on animal models for other cancers. The objective of this study was to determine the intraocular levels of carboplatin following intravenous administration of carboplatin in the treatment of human intraocular retinoblastoma. Eight patients with bilateral intraocular retinoblastoma were treated in a consistent fashion with intravenous carboplatin. One additional patient was similarly treated, but enucleated one month later. Samples were taken from those nine eyes after enucleation one to two hours after the administration of 18.7 mg/kg (560 mg/m( 2) for patients more than 12 kg) of intravenous carboplatin, and carboplatin concentrations in the aqueous and vitreous were then measured by atomic absorption spectrometry. The mean concentration measured in the aqueous was 5.13 microg/ml and in the vitreous 4.05 microg/ml, and vitreal concentrations were an average of 80% of aqueous concentrations. In one patient, a vitreous concentration of carboplatin was detected after an interval of one month that was 10% of the levels found in the samples enucleated one hour post-administration. These concentrations are much higher than previous animal studies would predict, and are similar to levels measured in unaffected animals when the drug is given after the use of cryotherapy. The concentration also approaches levels previously shown to be toxic to the retina. This elevation in carboplatin concentration may be due to disruption of the blood-vitreous barrier by active tumor.
以往关于卡铂向玻璃体渗透的研究依赖于未受影响的动物或其他癌症的动物模型。本研究的目的是确定在治疗人类眼内视网膜母细胞瘤时静脉注射卡铂后眼内卡铂的水平。8例双侧眼内视网膜母细胞瘤患者接受了一致方式的静脉卡铂治疗。另外1例患者也接受了类似治疗，但在1个月后进行了眼球摘除。在静脉注射18.7mg/kg（体重超过12kg的患者为560mg/m²）卡铂后1至2小时，从这9只摘除的眼球中取样，然后通过原子吸收光谱法测量房水和玻璃体中的卡铂浓度。房水中测得的平均浓度为5.13μg/ml，玻璃体中为4.05μg/ml，玻璃体浓度平均为房水浓度的80%。在1例患者中，给药1小时后摘除的样本中卡铂玻璃体浓度在1个月后检测到为其10%。这些浓度远高于以往动物研究的预测值，与使用冷冻疗法后给药时在未受影响动物中测得的水平相似。该浓度也接近先前显示对视网膜有毒性的水平。卡铂浓度的这种升高可能是由于活跃肿瘤破坏了血 - 玻璃体屏障。
