Document Detail


Pharmacokinetics of melphalan in isolated limb perfusion.
MedLine Citation:
PMID:  9923539     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pharmacokinetics of melphalan was studied by sampling of tissue and plasma in 72 rats that underwent isolated hyperthermic limb perfusion under different conditions. A miniaturized extracorporeal circulation system for small animals was used for perfusion of the rat hindlimb. Melphalan levels (L-phenylalanine mustard, L-PAM) were determined by high-performance liquid chromatography (HPLC). The temperature of the perfusate plasma and tissue, pH, administration method, and flow rate were modified and compared with regard to their influence on pharmacokinetic parameters. The highest tissue penetration of melphalan was observed under the following conditions: (a) pH range of the perfusate plasma between 7.3 and 7.7 (physiological environment), (b) temperature range of the perfusate from 40 degrees to 41.5 degrees C (destruction of cellular carrier systems at higher temperatures and increased inactivation by hydrolysis of melphalan above 41.5 degrees C), (c) application of melphalan as a single dose into the reservoir of the extracorporeal circuit (optimal tissue penetration), and (d) reduced perfusate flow (prolonged contact time between perfusate and tissue).
Authors:
A Norda; U Loos; M Sastry; J Goehl; W Hohenberger
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  43     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  1999  
Date Detail:
Created Date:  1999-02-05     Completed Date:  1999-02-05     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  35-42     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Knappschaft Hospital, Recklinghausen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Animals
Antineoplastic Agents, Alkylating / blood,  pharmacokinetics*
Area Under Curve
Chromatography, High Pressure Liquid
Extremities* / blood supply
Half-Life
Melphalan / blood,  pharmacokinetics*
Muscle, Skeletal / blood supply,  metabolism
Perfusion
Rats
Regional Blood Flow
Chemical
Reg. No./Substance:
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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