Toxicity and pharmacokinetics of isolated lung perfusion with cisplatin in rat

Abstract

Objective: This study was designed to evaluated the toxicity and the pharmacokinetics of cisplatin administered via isolated lung perfusion in Fischer 344 rat.Methods: 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.Results: 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 lugn was significantly higher than that in the lung of the animal treated intravenously (16.6±6.2 μg/g of tissue and 7.5±3.2 μg/g of tissue, respectively) (p=0.0096).Conclusion: Isolated lung perfusion with 3.3 mg/kg of cisplatin was pharmacokinetically superior to the maximum tolerated intravenous injection of cisplatin.