Pharmacokinetics after endovascular lung perfusion with cisplatin

PURPOSE: Endovascular lung perfusion (ELP) is a technique designed to deliver high doses of cisplatin via the pulmonary artery for the treatment of lung tumors. The purpose of the current study was to evaluate variables that affect adduct formation. MATERIALS AND METHODS: Thirteen swine underwent ELP. The first group (n = 6) underwent infusion of 150 mg cisplatin diluted to 0.5 mg/mL via a balloon occlusion catheter in the left pulmonary artery. Uptake was compared with that seen with systemic infusion. A second group (n = 7) underwent bilateral sequential infusion of the left pulmonary artery, followed by the right. Cisplatin (150 mg) was infused at one of three concentrations: 1 mg/mL (n = 5 lungs), 0.67 mg/mL (n = 5 lungs), or 0.5 mg/mL (n = 4 lungs). The Pearson coefficient was used to correlate uptake with infusion time, infusate concentration, animal weight, and initial mean pulmonary artery pressure. RESULTS: In the first group, cisplatin uptake in the control lung was less than 8% of that in the study lung. Infusion times for both groups ranged from 3 minutes to 56 minutes. Increases in infusion time correlated with increased adduct levels (r = 0.831; P < .0001). Mean uptake at concentrations of 0.5, 0.67, and 1 mg/mL were 25.79, 12.43, and 13.12 fmol/μg, respectively. There was no significant correlation between pulmonary adduct levels and infusate concentration (r = 0.106; P = .72). Animal weight and initial mean pulmonary artery pressure were not correlated with adduct formation. CONCLUSIONS: ELP with longer infusions of cisplatin may lead to greater adduct formation in pulmonary tissues. Changes in concentration of the infusate do not affect uptake of cisplatin. Hemodynamic parameters do not affect cisplatin uptake.