| Pharmacokinetics of melphalan in isolated limb perfusion. | |
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MedLine Citation:
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PMID: 9923539 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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). |
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Authors:
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A Norda; U Loos; M Sastry; J Goehl; W Hohenberger |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cancer chemotherapy and pharmacology Volume: 43 ISSN: 0344-5704 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 1999 |
Date Detail:
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Created Date: 1999-02-05 Completed Date: 1999-02-05 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: GERMANY |
Other Details:
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Languages: eng Pagination: 35-42 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Knappschaft Hospital, Recklinghausen, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Antineoplastic Agents, Alkylating; 148-82-3/Melphalan |
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