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

Michael S. Buss From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Buss, Henry, Tyler); the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610 (Tobias, Moore); the Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756 (Hoopes); and the Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6510 (Daoud).

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Carolyn J. Henry From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Buss, Henry, Tyler); the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610 (Tobias, Moore); the Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756 (Hoopes); and the Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6510 (Daoud).

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Jeff W. Tyler From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Buss, Henry, Tyler); the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610 (Tobias, Moore); the Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756 (Hoopes); and the Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6510 (Daoud).

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Karen S. Tobias From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Buss, Henry, Tyler); the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610 (Tobias, Moore); the Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756 (Hoopes); and the Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6510 (Daoud).

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Sayed Daoud From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Buss, Henry, Tyler); the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610 (Tobias, Moore); the Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756 (Hoopes); and the Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6510 (Daoud).

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Jack Hoopes From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Buss, Henry, Tyler); the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610 (Tobias, Moore); the Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756 (Hoopes); and the Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6510 (Daoud).

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Michael P. Moore From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Buss, Henry, Tyler); the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610 (Tobias, Moore); the Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756 (Hoopes); and the Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6510 (Daoud).

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Abstract

Objectives

To determine systemic and local platinum concentrations released from subcutaneously implanted cis-diamminedichloroplatinum (cisplatin)-impregnated polymethylmethacrylate (PMMA) and to evaluate systemic or local adverse 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 before implantation, at 3, 6, and 12 hours after implantation on day 0, and once daily on days 1, 2, 3, 7, 14, 21, and 29. At similar times on similar days, tissue chamber fluid samples also were obtained for platinum determination. 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 significantly greater than plasma and control site tissue chamber concentrations on days 2, 3, 7, 10. Mean plasma platinum concentration at 3 (0.735 µg/ml), 6 (0.691 µg/ml), 12 (0.534 µg/ml), 24 (0.131 µg/ml), 48 (0.2 µg/ml), 72 (0.1 µg/ml), and 158 (0.014 µg/ml) hours was significantly greater than pretreatment values (0.0 µg/ml). Plasma platinum concentration 10 days after treatment (0.011 µg/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 concentration of platinum was released locally relative to plasma concentration for an extended period. (Am J Vet Res 1999;60:280–283)

Abstract

Objectives

To determine systemic and local platinum concentrations released from subcutaneously implanted cis-diamminedichloroplatinum (cisplatin)-impregnated polymethylmethacrylate (PMMA) and to evaluate systemic or local adverse 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 before implantation, at 3, 6, and 12 hours after implantation on day 0, and once daily on days 1, 2, 3, 7, 14, 21, and 29. At similar times on similar days, tissue chamber fluid samples also were obtained for platinum determination. 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 significantly greater than plasma and control site tissue chamber concentrations on days 2, 3, 7, 10. Mean plasma platinum concentration at 3 (0.735 µg/ml), 6 (0.691 µg/ml), 12 (0.534 µg/ml), 24 (0.131 µg/ml), 48 (0.2 µg/ml), 72 (0.1 µg/ml), and 158 (0.014 µg/ml) hours was significantly greater than pretreatment values (0.0 µg/ml). Plasma platinum concentration 10 days after treatment (0.011 µg/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 concentration of platinum was released locally relative to plasma concentration for an extended period. (Am J Vet Res 1999;60:280–283)

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