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Pharmacokinetics of platinum and safety evaluation of carboplatin-impregnated calcium sulfate hemihydrate beads after implantation in healthy cats.
Vet Surg 2020VS

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/m2 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.

Authors+Show Affiliations

Department of Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida.Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, Illinois.Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama.Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, Illinois.Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, Illinois.Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, Illinois.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31944331

Citation

Maxwell, Elizabeth A., et al. "Pharmacokinetics of Platinum and Safety Evaluation of Carboplatin-impregnated Calcium Sulfate Hemihydrate Beads After Implantation in Healthy Cats." Veterinary Surgery : VS, 2020.
Maxwell EA, Phillips H, Clark-Price SC, et al. Pharmacokinetics of platinum and safety evaluation of carboplatin-impregnated calcium sulfate hemihydrate beads after implantation in healthy cats. Vet Surg. 2020.
Maxwell, E. A., Phillips, H., Clark-Price, S. C., Vieson, M. D., Selmic, L. E., Schaeffer, D. J., & Fan, T. M. (2020). Pharmacokinetics of platinum and safety evaluation of carboplatin-impregnated calcium sulfate hemihydrate beads after implantation in healthy cats. Veterinary Surgery : VS, doi:10.1111/vsu.13372.
Maxwell EA, et al. Pharmacokinetics of Platinum and Safety Evaluation of Carboplatin-impregnated Calcium Sulfate Hemihydrate Beads After Implantation in Healthy Cats. Vet Surg. 2020 Jan 16; PubMed PMID: 31944331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of platinum and safety evaluation of carboplatin-impregnated calcium sulfate hemihydrate beads after implantation in healthy cats. AU - Maxwell,Elizabeth A, AU - Phillips,Heidi, AU - Clark-Price,Stuart C, AU - Vieson,Miranda D, AU - Selmic,Laura E, AU - Schaeffer,David J, AU - Fan,Timothy M, Y1 - 2020/01/16/ PY - 2019/04/30/received PY - 2019/11/16/revised PY - 2019/12/08/accepted PY - 2020/1/17/entrez JF - Veterinary surgery : VS JO - Vet Surg N2 - 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/m2 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. SN - 1532-950X UR - https://www.unboundmedicine.com/medline/citation/31944331/Pharmacokinetics_of_platinum_and_safety_evaluation_of_carboplatin-impregnated_calcium_sulfate_hemihydrate_beads_after_implantation_in_healthy_cats L2 - https://doi.org/10.1111/vsu.13372 DB - PRIME DP - Unbound Medicine ER -