Experimental models of regional chemotherapy via the pulmonary artery using cisplatin

The pharmacokinetics of cisplatin was investigated in pigs according to the infusion route and administration modality. Twelve pigs were assigned to receive cisplatin (2.5 mg/kg) via the systemic vein, pulmonary artery, pulmonary artery with stop-flow, and pulmonary artery with stop-flow/outflow occlusion. Serial blood, lung parenchyma and mediastinal node samples were obtained before, at completion of, and 5, 15, 30, 60, 120, 180, and 240 min after infusion. Urine samples were collected 2 h and 2-4 h following drug administration. Specimens from thyroid, esophagus, heart, liver, spleen, adrenal gland, kidney and bone marrow were taken 4 h after treatment. Platinum concentrations in plasma, plasma ultrafiltrate, erythrocytes, tissues and urine were determined by flameless atomic absorption spectroscopy. Pulmonary artery infusion, with or without stop-flow, yielded no significant pharmacokinetic advantage with respect to the systemic vein administration. Instead, pulmonary artery infusion with stop-flow/outflow occlusion produced higher platinum concentrations in lung and mediastinal nodes and lower systemic plasma and tissue platinum levels.