Pharmacokinetic and safety assessment of carboplatin-impregnated calcium sulfate hemihydrate beads in eight rats.
Vet Surg
; 50(8): 1650-1661, 2021 Nov.
Article
em En
| MEDLINE
| ID: mdl-34375028
ABSTRACT
OBJECTIVE:
Evaluate local tissue toxicity and plasma platinum (Pt) in vivo after subcutaneous implantation of carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads. STUDYDESIGN:
In vivo experimental study. ANIMALS Eight male Sprague-Dawley rats.METHODS:
CI-CSH beads were implanted subcutaneously (5 mg carboplatin/rat; 13.5 mg/kg carboplatin; 7.08 mg/kg Pt; 1.18 mg/m2 Pt) in eight rats (d0). Wound healing (daily), radiographic bead dissolution (weekly), systemic Pt uptake (plasma-Pt), local tissue Pt (d28), and histologic changes compared to nonincised and incised catheterization sites (d28) were assessed. Blood and tissue samples were analyzed by inductively coupled plasma mass spectrometry for Pt, and pharmacokinetic analysis was performed using noncompartmental methods.RESULTS:
One rat died at d10, the remainder survived until d28. No wound complications were seen. The CI-CSH implantation site had higher histopathology scores than the other sites for necrosis (p = .013) and fibrosis (p = .013). Beads decreased in density radiographically (d0 to d28) (p = .062). Peak plasma-Pt concentration was 225.78 ng/ml at 12 h, and decreased over time, but Pt was still detectable on d28. The elimination half-life was 5.03 ± 1.13 days. Only 1.69% of implanted Pt remained in the beads at d28.CONCLUSIONS:
CI-CSH beads incited microscopic mild inflammation but wound healing was not impaired. Pt was absorbed systemically and the release from the beads was near complete at d28. CLINICALSIGNIFICANCE:
Piled CI-CSH bead implantation is well tolerated in rats with similar elution profile as previously described. Beads were radiographically visible at d28. Minimal Pt was detected systemically suggesting Pt release does not match bead dissolution.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Platina
/
Sulfato de Cálcio
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article