Pharmacokinetics of platinum and safety evaluation of carboplatin‐impregnated calcium sulfate hemihydrate beads after implantation in healthy cats. Issue 4 (16th January 2020) - Maxwell, Elizabeth A.
Abstract: Objective: To evaluate the pharmacokinetics (PK) of platinum (Pt) and safety of carboplatin‐impregnated calcium sulfate hemihydrate (C‐I CSH) beads after implantation in healthy cats. Study design: In vivo experimental study. Animals: Six healthy adult cats. Methods: Three C‐I CSH beads were implanted in muscle pockets over the right and left hemithoraces of each cat (~3.9 mg/kg of Pt; 60.4 mg/m 2 of calculated carboplatin). Hematology and blood chemistry were tested at baseline and 3, 7, 14, and 21 days postimplantation. Serum was analyzed for Pt at specific times from 1 hour to 21 days. Tissue was obtained for histopathology and analysis of Pt at 3, 7, 14, and 21 days at standardized distances from implantation sites. Results: Platinum was detected in tissues at all times and distances (range, 0.1‐4.19 μg/g). Serum Pt increased up to 2.6 hours (3.25 μg/mL) then decreased sharply. Samples containing muscle had higher Pt compared with samples without muscle ( P = .004). Mild hypercalcemia was noted in four cats, and mild inflammatory reaction was noted on histopathology of all samples. Conclusion: Platinum was released from C‐I CSH beads differentially into surrounding tissues over 21 days. Systemic absorption of Pt was minimal, but mild hypercalcemia occurred. Clinical significance: Implantation was well tolerated by healthy adult cats. Securing beads within muscle may limit Pt diffusion to targeted tissue. Although Pt concentrations did not achieve levels reported to be cytotoxic for feline sarcoma cells in culture, results provide evidence to support evaluation of efficacy in the tumor microenvironment of cats with locally invasive cancers.