Regional differences of melphalan lung levels after isolated lung perfusion in the rat

BACKGROUND: Efficacy studies of isolated lung perfusion (ILuP) with melphalan showed superior results compared to intravenous therapy. However, the influence of pharmacokinetic parameters on the final melphalan lung concentration (FMLC) is unknown. In this study, we studied the impact of three different perfusion parameters on the FMLC in different areas of the lung. MATERIAL AND METHODS: Fifty-four rats were randomized into nine groups. Each group underwent ILuP with variation of perfusion duration (15, 30, and 60 min), the flow (0.125, 0.25, and 0.5 ml/min), concentration (8.3, 16.7, 33.3, 66.7, and 133.3 microg/ml) and the resulting dose (maximum 4 mg/kg). Lung samples were taken from the hilum and at the periphery of the lung (apex, base). Additional samples were taken to evaluate wet-to-dry ratio (W/D-ratio). Multiple linear regression and Student's t test were used for analysis. Significance was defined as a P