title: Regional differences of melphalan lung levels after isolated lung perfusion in the rat.
abstract: 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.
  
  
  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<or=0.05.
  
  
  RESULTS
  Experiment 1: The W/D-ratio was not influenced by varying the perfusion parameters (P=0.97). Experiment 2: multiple regression led to an equation that predicts FMLC for each area of the lung studied. FMLC is dependent on concentration, perfusion time, and region.
  
  
  CONCLUSIONS
  The influence of the perfusion parameters on FMLC is dependent on the area of the lung perfused. This should be taken into consideration when pulmonary metastases are treated with ILuP.
authors.affiliation: Laboratory for Experimental Surgery, University of Antwerp, Wilrijk, Belgium. sanderromijn@wanadoo.nl
authors.forename: Sander
authors.initials: S
authors.lastname: Romijn
authors.forename: Jeroen M H
authors.initials: JM
authors.lastname: Hendriks
authors.forename: Bart P
authors.initials: BP
authors.lastname: Van Putte
authors.forename: Joost
authors.initials: J
authors.lastname: Weyler
authors.forename: Gunther
authors.initials: G
authors.lastname: Guetens
authors.forename: Gert
authors.initials: G
authors.lastname: De Boeck
authors.forename: Paul E Y
authors.initials: PE
authors.lastname: Van Schil
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010478:Chemotherapy, Cancer, Regional Perfusion; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D016014:Linear Models; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan