Document Detail


Modified approach of administering cytostatics to the lung: more efficient isolated lung perfusion.
MedLine Citation:
PMID:  16928530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Bart P van Putte; Jeroen M H Hendriks; Gunther Guetens; Gert de Boeck; Ernst A de Bruijn; Paul E Y van Schil; Gert Folkerts
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  82     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-24     Completed Date:  2006-09-13     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1033-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiothoracic Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands. bvanputte@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimetabolites, Antineoplastic / administration & dosage*,  analysis,  pharmacokinetics
Chemotherapy, Cancer, Regional Perfusion / instrumentation,  methods*
Chromatography, High Pressure Liquid
Deoxycytidine / administration & dosage,  analogs & derivatives*,  analysis,  pharmacokinetics
Diffusion
Lung / chemistry,  drug effects*
Lung Neoplasms / drug therapy*
Male
Models, Biological
Rats
Rats, Wistar
Spectrophotometry, Ultraviolet
Therapeutic Irrigation
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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