Kaneda Y, Liu D, Brooks A, Abolhoda A, Labow D, Burt M E, Ginsberg R J
Department of Surgery I, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Jpn J Thorac Cardiovasc Surg. 2001 Jul;49(7):443-8. doi: 10.1007/BF02913910.
This study was designed to evaluate the toxicity and the pharmacokinetics of cisplatin administered via isolated lung perfusion in Fischer 344 rat.
Toxicity study; Cisplatin dosages of 3.3, 5.0, 6.7, and 10.0 mg/kg were injected intravenously in four groups, respectively. Cisplatin dosages of 3.3, 5.0, and 6.7 mg/kg were perfused via isolated lung perfusion in a further three groups, respectively. The maximum tolerated dosage of cisplatin was determined by assessing the survival rate on day 21. Pharmacokinetics study; Animals received 6.7 mg/kg of cisplatin intravenously or 3.3 mg/kg of cisplatin via isolated lung perfusion. The cisplatin levels of the lung were measured by flameless atomic spectrometry.
Toxicity study; The maximum tolerated dosage of cisplatin via intravenous injection was 6.7 mg/kg, and via isolated lung perfusion was 3.3 mg/kg. Pharmacokinetics study; The cisplatin level in the perfused lung was significantly higher than that in the lung of the animal treated intravenously (16.6 +/- 6.2 micrograms/g of tissue and 7.5 +/- 3.2 micrograms/g of tissue, respectively) (p = 0.0096).
Isolated lung perfusion with 3.3 mg/kg of cisplatin was pharmacokinetically superior to the maximum tolerated intravenous injection of cisplatin.
本研究旨在评估顺铂经离体肺灌注给药在Fischer 344大鼠中的毒性和药代动力学。
毒性研究；分别将3.3、5.0、6.7和10.0mg/kg剂量的顺铂静脉注射到四组大鼠体内。另外三组分别经离体肺灌注3.3、5.0和6.7mg/kg剂量的顺铂。通过评估第21天的存活率来确定顺铂的最大耐受剂量。药代动力学研究；动物静脉注射6.7mg/kg顺铂或经离体肺灌注3.3mg/kg顺铂。通过无火焰原子光谱法测量肺中的顺铂水平。
毒性研究；静脉注射顺铂的最大耐受剂量为6.7mg/kg，经离体肺灌注的最大耐受剂量为3.3mg/kg。药代动力学研究；灌注肺中的顺铂水平显著高于静脉注射治疗动物肺中的顺铂水平（分别为16.6±6.2μg/g组织和7.5±3.2μg/g组织）（p = 0.0096）。
3.3mg/kg顺铂经离体肺灌注在药代动力学上优于顺铂最大耐受静脉注射。
