Effect of tumor presence on cisplatin and carboplatin: disposition in the isolated, perfused tumor and skin flap.
The purpose of this study was to evaluate the disposition of elemental platinum (Pt) derived from cisplatin (CDDP) or carboplatin (CBDCA) in the isolated, perfused tumor and skin flap (IPTSF). Flaps were perfused with either 3.0 micrograms CDDP/ml perfusion medium (n = 4 tumor, n = 4 control) or 15 micrograms CBDCA/ml (n = 4 tumor, n = 3 control) at a rate of 1 ml/min for 3 h. A 2-h (CDDP experiments) or 3-h (CBDCA experiments) washout phase using undosed medium was then performed. The disposition kinetics of free (ultrafilterable) Pt were characterized using a four-compartment physiologically relevant pharmacokinetic model. A tumor effect on the disposition of Pt was noted in that the Pt mass from CDDP in the central and mobile tissue compartments was greater in tumor flaps than in control flaps (P < 0.05). Similar trends were noted in CBDCA-treated flaps, but these were not significant. The Pt mass in the fixed tumor and non-tumor tissue compartments was significantly greater when Pt was derived from CDDP than when it was derived from CBDCA (P < 0.05). A linear relationship existed between the estimated micrograms of Pt in the flaps from both CDDP and CBDCA and the cross-sectional vascular resistance of the flaps at 30 (CDDP, r = 0.78; CBDCA, r = 0.89) and 60 min (CDDP, r = 0.65; CBDCA, r = 0.85) of perfusion. We conclude that the IPTSF is a useful model for evaluating the disposition of Pt drugs in tumor and non-tumor tissue and that tumor presence alters the disposition of CDDP.
Vaden
S L
SL
Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Williams
P L
PL
Page
R L
RL
Riviere
J E
JE
D000818:Animals; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000295:instrumentation; D002822:Choriocarcinoma; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008954:Models, Biological; D010984:Platinum / Q000032:analysis; D012867:Skin / Q000378:metabolism*; D013552:Swine; D014407:Tumor Cells, Cultured / Q000378:metabolism*; D014655:Vascular Resistance
D010984:Platinum; D016190:Carboplatin; D002945:Cisplatin