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.


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.
Romijn
Sander
S
Laboratory for Experimental Surgery, University of Antwerp, Wilrijk, Belgium. sanderromijn@wanadoo.nl
Hendriks
Jeroen M H
JM
Van Putte
Bart P
BP
Weyler
Joost
J
Guetens
Gunther
G
De Boeck
Gert
G
Van Schil
Paul E Y
PE
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
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan