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.