Flow, perfusion time and the concentration of perfusate do not influence the final concentration of melphalan in the lung after isolated lung perfusion in rats
S. Romijn, J. M. H. Hendriks, B. P. Van Putte, P. E. Y. Van Schil (Edegem, Belgium)
Source: Annual Congress 2002 - Isolated lung perfusion and lung cancer
Session: Isolated lung perfusion and lung cancer
Session type: Oral Presentation
Number: 1149
Abstract OBJECTIVE: Isolated lung perfusion (ILuP) with melphalan (MN) is superior to intravenous infusion in an experimental rat model for the treatment of pulmonary carcinoma and sarcoma metastases. We studied the influence of flow, perfusion time and concentration on melphalan lung levels in our rat model of isolated lung perfusion. METHODS: To Determine the level at which the lung is saturated by MN, ILuP was performed in WAG/Rij rats during 30 minutes by a single pass system with 0.5 mg (n=5), 0.05 mg (n=5), 0.01 mg (n=5) and 0.005 mg (n=5) of MN. In a second experiment, the influence of flow, perfusion time and concentration was analyzed using the dose beneath saturation found in the first experiment. Lung perfusion was performed during 30 minutes with a flow of 0.5 mL/min (n=4), during 60 minutes with a flow of 0.5 mL/min (n=4) and during 30 minutes with a flow of 1.0 mL/min (n=4). For comparison of melphalan lung levels the unpaired Student's T-test was applied. Statistical significance was reached at p<0,05. RESULTS: Melphalan lung levels of rats perfused with 0.5 mg (89.7±]47mg/g) and 0.05 mg (25±]0.3 mg/g) were significantly higher compared to the lower doses (0.01mg: 0.6±]0.3mg/g; 0.005mg: 1.4±]0.2mg/g). Perfusions performed with 0.5 mg were at a saturated level. Therefore 0.05 mg was chosen as the dose for the second experiment. No significant differences were seen in lung levels of MN between the groups with variation in perfusion time, flow and concentration. CONCLUSION: since no influence of flow, perfusion time and concentration was observed with a dose of 0.05 mg of MN, the only determinant of final lung MN levels is the dose administered. Consequently, MN can be given as a dose in the perfusion circuit or a concentration by single-pass perfusion.
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S. Romijn, J. M. H. Hendriks, B. P. Van Putte, P. E. Y. Van Schil (Edegem, Belgium). Flow, perfusion time and the concentration of perfusate do not influence the final concentration of melphalan in the lung after isolated lung perfusion in rats. Eur Respir J 2002; 20: Suppl. 38, 1149
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