Article
 

Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma

Public Deposited

Contenu téléchargeable

Télécharger le fichier PDF
https://ir.library.oregonstate.edu/concern/articles/m900nv184

Descriptions

Attribute NameValues
Creator
Abstract
  • Background: Osteosarcoma in dogs and humans share many similarities and the dog has been described as an excellent model to study this disease. The median survival in dogs has not improved in the last 25 years. Taurolidine has been shown to be cytotoxic to canine and human osteosarcoma in vitro. The goals of this study were to determine the pharmacokinetics and safety of taurolidine in healthy dogs and the safety of taurolidine in combination with doxorubicin or carboplatin in dogs with osteosarcoma. Methods: Two percent taurolidine was infused into six healthy dogs (150 mg/kg) over a period of two hours and blood samples were taken periodically. One dog received taurolidine with polyvinylpyrrolidone (PVP) as its carrier and later received PVP-free taurolidine as did all other dogs in this study. Serum taurolidine concentrations were determined using high-performance liquid chromatography (HPLC) online coupled to ESI-MS/MS in the multiple reaction monitoring mode. Subsequently, the same dose of taurolidine was infused to seven dogs with osteosarcoma also treated with doxorubicin or carboplatin. Results: Taurolidine infusion was safe in 6 healthy dogs and there were no significant side effects. Maximum taurolidine serum concentrations ranged between 229 to 646 μM. The dog that received taurolidine with PVP had an immediate allergic reaction but recovered fully after the infusion was stopped. Three additional dogs with osteosarcoma received doxorubicin and taurolidine without PVP. Toxicities included dilated cardiomyopathy, protein-losing nephropathy, renal insufficiency and vasculopathy at the injection site. One dog was switched to carboplatin instead of doxorubicin and an additional 4 dogs with osteosarcoma received taurolidine-carboplatin combination. One incidence of ototoxicity occurred with the taurolidine- carboplatin combination. Bone marrow and gastro-intestinal toxicity did not appear increased with taurolidine over doxorubicin or carboplatin alone. Conclusions: Taurolidine did not substantially exacerbate bone marrow or gastro-intestinal toxicity however, it is possible that taurolidine increased other toxicities of doxorubicin and carboplatin. Administering taurolidine in combination with 30 mg/m2 doxorubicin in dogs is not recommended but taurolidine in combination with carboplatin (300 mg/m2) appears safe.
  • Keywords: Taurolidine, Osteosarcoma, Carboplatin, Doxorubicin, Dog
Resource Type
DOI
Date Available
Date Issued
Citation
  • Marley, K., Helfand, S., Simpson, J., Mata, J., Tracewell, W., Brownlee, L., . . . Seguin, B. (2013). Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma. Journal of Experimental & Clinical Cancer Research, 32(1), 74-74. doi:10.1186/1756-9966-32-74
Journal Title
Journal Volume
  • 32
Academic Affiliation
Déclaration de droits
Funding Statement (additional comments about funding)
  • Thisstudy was partly funded by Morris Animal foundation grant #D07CA-070 to BSand SCH, The Department of Clinical Sciences, College of Veterinary Medicine,Oregon State University, the Gabriel Institute (www.gabrielinstitute.org), and adonation from Dr. Joanne Wisniewski.
Publisher
Peer Reviewed
Language
Replaces

Des relations

Parents:

This work has no parents.

Articles

La vignette Titre Date de téléchargement Visibilité actes
file details MarleyKevinVeterinaryMedicinePharmacokineticStudyEvaluation.pdf 2017-07-13 Public Télécharger