An in vitro-in vivo validation of the isolated perfused tumor and skin flap preparation as a model of cisplatin delivery to tumors.
The isolated perfused tumor and skin flap (IPTSF) is a unique model system in which drug disposition is evaluated in tumor tissue and surrounding normal tissue, both of which are supplied by the same vascular system. We compared tissue Pt concentrations obtained following systemic administration of cisplatin (CDDP) to whole pigs bearing tumored skin flaps with data obtained from IPTSF treated similarly. During the in vivo study, CDDP was administered intravenously to six pigs that had tumor and skin flaps. IPTSF were created in four pigs and isolated in a perfusion chamber and perfused with medium containing CDDP for 180 min. Venous plasma or perfusate samples were serially collected throughout perfusion. Tissue samples were collected after perfusion was complete. All samples were assayed for Pt by atomic absorption spectroscopy. Area under the curve of Pt profiles from IPTSF and in vivo perfused flaps were not significantly different. Pt concentrations were significantly higher in tumor samples from in vivo perfused flaps than in samples from IPTSF. Pt concentrations in skin and subcutaneous tissue were not significantly different. When consideration is given to all of the potential variables that were operative in these experiments, the results of this study demonstrate that Pt distribution within the IPTSF was comparable to that obtained in vivo.
Vaden
S L
SL
Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Page
R L
RL
Riviere
J E
JE
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor; D066298:In Vitro Techniques; D015552:Injections, Intralesional; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D015203:Reproducibility of Results; D013524:Surgical Flaps; D013552:Swine
D000970:Antineoplastic Agents; D002945:Cisplatin