| Reduced liver uptake of arterially infused melphalan during retrograde rat liver perfusion with unaffected liver tumor uptake. | |
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MedLine Citation:
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PMID: 12388659 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Isolated hepatic perfusion (IHP) with melphalan is used for patients with nonresectable metastases confined to the liver. To improve the efficacy of IHP and to reduce the toxicity to the liver, reversion (retrograde perfusion) of the bloodstream through the liver in a rat model was studied. For liver tumor induction male WAG/Rij rats were inoculated with CC531 cells, a colorectal tumor cell line. After 11 to 12 days the tumor-bearing rat livers were perfused by single-pass perfusion through either the portal (orthograde) or caval vein (retrograde) for different time periods. During perfusion melphalan (160 Schultze) was infused in the hepatic artery. Melphalan concentrations were measured by high-performance liquid chromatography. A rapid extraction of melphalan by the liver occurred in the first 5 min, reaching steady state after 10 to 20 min for both perfusion directions. The melphalan concentration of the outflow perfusate was significantly higher in the retrograde perfusion compared with the orthograde perfusion. The melphalan content of the tumor tissue was unaffected by perfusion direction at any time point. To the contrary, the melphalan uptake in liver tissue was strongly influenced: the melphalan content after 40-min retrograde perfusion was 12% of that after orthograde perfusion. The average tumor/liver concentration ratio was 6 for orthograde perfusion and 30 for retrograde perfusion. In conclusion, retrograde IHP with continuous melphalan infusion in the hepatic artery provides a high tumor uptake of melphalan with potentially reduced liver toxicity compared with orthograde IHP. |
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Authors:
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Joost Rothbarth; Rolf W Sparidans; Jos H Beijnen; Leo J Schultze-Kool; Hein Putter; Cornelis J H van de Velde; Gerard J Mulder |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 303 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-10-21 Completed Date: 2002-11-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 736-40 Citation Subset: IM |
Affiliation:
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Department of Surgery, Leiden/Amsterdam Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents, Alkylating / administration & dosage, pharmacokinetics, pharmacology* Chromatography, High Pressure Liquid Hepatic Artery Infusions, Intravenous Liver / metabolism* Liver Neoplasms / metabolism* Male Melphalan / administration & dosage, pharmacokinetics, pharmacology* Neoplasm Transplantation Perfusion Rats Rats, Inbred Strains |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Alkylating; 148-82-3/Melphalan |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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