title: The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft.
abstract: An isolated rat hindlimb perfusion model carrying xenografts of the human melanoma cell line MM96 was used to study the effects of perfusion conditions on melphalan distribution. Krebs-Henseleit buffer and Hartmann's solution containing 4.7% bovine serum albumin (BSA) or 2.8% dextran 40 were used as perfusates. Melphalan concentrations in perfusate, tumour nodules and normal tissues were measured using high-performance liquid chromatography (HPLC). Increasing the perfusion flow rates (from 4 to 8 ml min(-1)) resulted in higher tissue blood flow (determined with 51Cr-labelled microspheres) and melphalan uptake by tumour and normal tissues. The distribution of melphalan within tumour nodules and normal tissues was similar for both Krebs-Henseleit buffer and Hartmann's solution; however, tissue concentrations of melphalan were significantly higher for a perfusate containing 2.8% dextran 40 than for one containing 4.7% BSA. The melphalan concentration in the tumour was one-third of that found in the skin if the perfusate contained 4.7% BSA. In conclusion, this study has shown that a high perfusion flow enhances the delivery of melphalan into implanted tumour nodules and normal tissues, and a perfusate with low melphalan binding (no albumin) is preferred for maximum uptake of drug by the tumour.
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: P G
authors.initials: PG
authors.lastname: Parsons
authors.forename: M S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics*; D017690:Cell Transplantation; D002851:Chromatography, High Pressure Liquid; D005947:Glucose / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D008558:Melphalan / Q000493:pharmacokinetics*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D051381:Rats; D011923:Rats, Nude; D000077325:Ringer's Lactate; D014183:Transplantation, Heterologous; D014325:Tromethamine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007552:Isotonic Solutions; C074097:Krebs-Henseleit solution; D019188:Organ Preservation Solutions; D000077325:Ringer's Lactate; D014325:Tromethamine; D005947:Glucose; D008558:Melphalan