Effect of tumor presence on cisplatin and carboplatin: disposition in the isolated, perfused tumor and skin flap

Publisher Website
Google Scholar
Abstract
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 μg CDDP/ml perfusion medium (n=4 tumor,n=4 control) or 15 μg 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 (PPr=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.