title: Can tissue drug concentrations be monitored by microdialysis during or after isolated limb perfusion for melanoma treatment?
abstract: Isolated limb perfusion (ILP) with melphalan is used to treat recurrent melanoma. This study aimed to develop a microdialysis technique for melphalan tissue concentration measurement during ILP. The effects of melphalan concentration (50-600 microg/ml), microdIalysis flow rate (0.55-17.5 microl/min), probe length (5-50 mm) and temperature (25-41.5 degrees C) on in vitro recovery were studied. In addition, in vivo recovery was measured in rat hindlimbs perfused with melphalan using 50 mm microdialysis probes implanted subcutaneously and into muscle. Both dialysate and tissue sample melphalan concentrations were determined by high performance liquid chromatography. The in vitro recovery of melphalan was not affected by melphalan concentration or temperature, but increased with probe length and decreased with flow rate. The melphalan concentrations in subcutaneous and muscle dialysates were not significantly different. A linear relationship was found between tissue dialysate concentrations and actual tissue concentrations of melphalan (r2 = 0.97). Microdialysis is a potential method for tissue drug monitoring which may assist in the efficacious use of cytotoxics in human ILP.
authors.affiliation: Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Wu
authors.forename: B M
authors.initials: BM
authors.lastname: Smithers
authors.forename: C
authors.initials: C
authors.lastname: Anderson
authors.forename: M S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000818:Animals; D010478:Chemotherapy, Cancer, Regional Perfusion; D016903:Drug Monitoring / Q000379:methods*; D006614:Hindlimb; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D008558:Melphalan / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017551:Microdialysis / Q000379:methods*; D009379:Neoplasms, Muscle Tissue / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D008558:Melphalan