Modified approach of administering cytostatics to the lung: more efficient isolated lung perfusion.
BACKGROUND
Isolated lung perfusion (ILuP) is an experimental technique for the treatment of pulmonary metastases. We hypothesized that part of the drug taken up by the lung during ILuP is washed out during the flush procedure. Therefore, we investigated gemcitabine uptake at different inflow concentrations, and the effect of delayed clamp release after ILuP on lung levels was studied.


METHODS
Thirty rats had ILuP during 30 minutes using gemcitabine perfusate levels of 1.3, 2.7, 4.0, 5.3, and 6.7 mg/mL. Another 37 rats underwent ILuP with gemcitabine perfusate levels of 6.7 mg/mL during 6 minutes followed by a 5-minute flush and 30 or 60 minutes of reperfusion, while two other groups had ILuP and delayed clamp release for 30 or 60 minutes followed by a 5-minute flush. All effluent and lung samples were stored for later analysis. Results were evaluated using Friedmann two-way analysis and two-way analysis of variance.


RESULTS
At 6 minutes, steady-state of gemcitabine uptake was achieved for all inflow concentrations and a linear relation (r = 0.933, p < 0.0001) between effluent and lung levels was observed. Delayed clamp release resulted in significantly higher lung levels compared with immediate restoration of blood circulation after ILuP (456% at 30 minutes and 828% at 60 minutes).


CONCLUSIONS
Effective gemcitabine lung levels are already achieved after 6 minutes of ILuP with 6.7 mg/mL followed by delayed clamp release during 30 minutes instead of the clinically applied 30 minutes ILuP.
van Putte
Bart P
BP
Department of Cardiothoracic Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands. bvanputte@yahoo.com
Hendriks
Jeroen M H
JM
Guetens
Gunther
G
de Boeck
Gert
G
de Bruijn
Ernst A
EA
van Schil
Paul E Y
PE
Folkerts
Gert
G
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000295:instrumentation / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D004058:Diffusion; D008168:Lung / Q000737:chemistry / Q000187:drug effects*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D007507:Therapeutic Irrigation; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine