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

http://ir.library.oregonstate.edu/concern/defaults/m900nv184

This is the publisher’s final pdf. The published article is copyrighted by BioMed Central Ltd. and can be found at:  http://www.biomedcentral.com/.

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • 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.
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
Academic Affiliation
Series
Keyword
Rights Statement
Funding Statement (additional comments about funding)
Publisher
Peer Reviewed
Language
Replaces
Additional Information
  • description.provenance : Approved for entry into archive by Deborah Campbell(deborah.campbell@oregonstate.edu) on 2013-11-25T17:43:15Z (GMT) No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) MarleyKevinVeterinaryMedicinePharmacokineticStudyEvaluation.pdf: 443046 bytes, checksum: b70572b0cb8145b43f786c0a1c3f95bd (MD5)
  • description.provenance : Made available in DSpace on 2013-11-25T17:43:15Z (GMT). No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) MarleyKevinVeterinaryMedicinePharmacokineticStudyEvaluation.pdf: 443046 bytes, checksum: b70572b0cb8145b43f786c0a1c3f95bd (MD5) Previous issue date: 2013-10-11
  • description.provenance : Submitted by Deborah Campbell (deborah.campbell@oregonstate.edu) on 2013-11-25T17:27:49Z No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) MarleyKevinVeterinaryMedicinePharmacokineticStudyEvaluation.pdf: 443046 bytes, checksum: b70572b0cb8145b43f786c0a1c3f95bd (MD5)

Relationships

In Administrative Set:
Last modified: 07/13/2017

Downloadable Content

Download PDF
Citations:

EndNote | Zotero | Mendeley

Items