Systemic and tissue chamber fluid platinum concentrations released from cis-diamminedichloroplatinum II-impregnated polymethylmethacrylate in healthydogs

Objectives-To determine systemic and local platinum concentrations released from subcutaneously implanted cis-diamminedichloroplatinum (cisplatin) -im pregnated polymethylmethacrylate (PMMA) and to evaluate systemic or local a dverse reactions. Animals-6 healthy dogs. Procedure-Cisplatin (20 mg) was inserted into PMMA that was fashioned into cylinders and placed into subcutaneous tissue chambers overlying the thorax (treated site). An empty tissue chamber was placed over the opposite side (control site). Plasma samples were obtained for platinum determination bef ore implantation, at 3, 6, and 12 hours after implantation on day 0, and on ce daily on days 1, 2, 3, 7, 14, 21, and 29. At similar times on similar da ys, tissue chamber fluid samples also were obtained for platinum determinat ion. Complete blood count, serum urea nitrogen and creatinine concentration determinations, and urinalyses were performed on days 1, 2, 3, 7, 14, 21, and 29. Complete necropsy was performed at conclusion of the study. Results-Tissue chamber platinum concentrations at the treated site were sig nificantly greater than plasma and control site tissue chamber concentratio ns on days 2, 3, 7, 10. Mean plasma platinum concentration at 3 (0.735 mu g /ml), 6 (0.691 mu g/ml), 12 (0.534 mu g/ml), 24 (0.131 mu g/ml), 48 (0.2 mu g/ml), 72 (0.1 mu g/ml), and 158 (0.014 mu g/ml) hours was significantly g reater than pretreatment values (0.0 mu g/ml). Plasma platinum concentratio n 10 days after treatment (0.011 mu g/ml) did not significantly differ from pretreatment values. Local or systemic adverse reactions were not apparent . Conclusions-The route of cisplatin administration was safe. Greater concent ration of platinum was released locally relative to plasma concentration fo r an extended period.