Cancer Chemotherapy and Pharmacology

, Volume 43, Issue 1, pp 35–42 | Cite as

Pharmacokinetics of melphalan in isolated limb perfusion

  • A. Norda
  • U. Loos
  • M. Sastry
  • J. Goehl
  • W. Hohenberger
ORIGINAL ARTICLE

Abstract

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° to 41.5 °C (destruction of cellular carrier systems at higher temperatures and increased inactivation by hydrolysis of melphalan above 41.5 °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).

Key words Melphalan Pharmacokinetics Hyperthermic limb perfusion Melanoma 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • A. Norda
    • 1
  • U. Loos
    • 1
  • M. Sastry
    • 1
  • J. Goehl
    • 2
  • W. Hohenberger
    • 2
  1. 1.Department of Internal Medicine, Knappschaft Hospital, Academic Teaching Hospital, D-45655 Recklinghausen, Germany Tel.: +49-2361-56-3401, Fax: +49-2361-56-3498DE
  2. 2.Department of Surgery, University of Erlangen-Nürnberg, D-91054 Erlangen, GermanyDE

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