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Vincristine chemotherapy trials and pharmacokinetics in tasmanian devils with tasmanian devil facial tumor disease.

Phalen DN, Frimberger A, Pyecroft S, Peck S, Harmsen C, Lola S, de Mello Mattos B, Li KM, McLachlan AJ, Moore A - PLoS ONE (2013)

Bottom Line: A dosage rate of 0.105 mg/kg, a rate significantly higher than that given in humans or domestic animals, was found to the highest dosage rate that could be administered safely.Plasma clearance (1.8 ml/min/kg) was slower in the Tasmanian devil than in humans, suggesting that pharmacodynamics and not pharmacokinetics explain the Tasmanian devil's ability to tolerate high dosage rates of vincristine.While providing base-line data for the use of vincristine in Tasmanian devils and possibly other marsupials with vincristine susceptible cancers, these findings strongly suggest that vincristine will not be effective in the treatment of DFTD.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Veterinary Science, University of Sydney, Sydney, New South Wales, Australia. david.phalen@sydney.edu.au

ABSTRACT
Tasmanian Devil Facial Tumor Disease (DFTD) is a transmissible cancer threatening to cause the extinction of Tasmanian Devils in the wild. The aim of this study was to determine the susceptibility of the DFTD to vincristine. Escalating dosage rates of vincristine (0.05 to 0.136 mg/kg) were given to Tasmanian devils in the early stages of DFTD (n = 8). None of these dosage rates impacted the outcome of the disease. A dosage rate of 0.105 mg/kg, a rate significantly higher than that given in humans or domestic animals, was found to the highest dosage rate that could be administered safely. Signs of toxicity included anorexia, vomiting, diarrhea and neutropenia. Pharmacokinetic studies showed that, as with other species, there was a rapid drop in blood concentration following a rapid intravenous infusion with a high volume of distribution (1.96 L/kg) and a relatively long elimination half life (11 h). Plasma clearance (1.8 ml/min/kg) was slower in the Tasmanian devil than in humans, suggesting that pharmacodynamics and not pharmacokinetics explain the Tasmanian devil's ability to tolerate high dosage rates of vincristine. While providing base-line data for the use of vincristine in Tasmanian devils and possibly other marsupials with vincristine susceptible cancers, these findings strongly suggest that vincristine will not be effective in the treatment of DFTD.

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Related in: MedlinePlus

Median plasma vincristine concentration versus time for Tasmanian devils (n = 6) corrected for a dose of vincristine 0.05 mg/kg.
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Related In: Results  -  Collection


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pone-0065133-g001: Median plasma vincristine concentration versus time for Tasmanian devils (n = 6) corrected for a dose of vincristine 0.05 mg/kg.

Mentions: Pharmacokinetic parameters for vincristine in the Tasmanian Devil are presented in Table 3. Figure 1 shows the median plasma vincristine concentration-time profiles of vincristine at a dosage rate of 0.05 mg/kg in the Tasmanian Devil. As expected there was an initial rapid decline in vincristine plasma concentrations, which was consistent with the distribution phase.


Vincristine chemotherapy trials and pharmacokinetics in tasmanian devils with tasmanian devil facial tumor disease.

Phalen DN, Frimberger A, Pyecroft S, Peck S, Harmsen C, Lola S, de Mello Mattos B, Li KM, McLachlan AJ, Moore A - PLoS ONE (2013)

Median plasma vincristine concentration versus time for Tasmanian devils (n = 6) corrected for a dose of vincristine 0.05 mg/kg.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675106&req=5

pone-0065133-g001: Median plasma vincristine concentration versus time for Tasmanian devils (n = 6) corrected for a dose of vincristine 0.05 mg/kg.
Mentions: Pharmacokinetic parameters for vincristine in the Tasmanian Devil are presented in Table 3. Figure 1 shows the median plasma vincristine concentration-time profiles of vincristine at a dosage rate of 0.05 mg/kg in the Tasmanian Devil. As expected there was an initial rapid decline in vincristine plasma concentrations, which was consistent with the distribution phase.

Bottom Line: A dosage rate of 0.105 mg/kg, a rate significantly higher than that given in humans or domestic animals, was found to the highest dosage rate that could be administered safely.Plasma clearance (1.8 ml/min/kg) was slower in the Tasmanian devil than in humans, suggesting that pharmacodynamics and not pharmacokinetics explain the Tasmanian devil's ability to tolerate high dosage rates of vincristine.While providing base-line data for the use of vincristine in Tasmanian devils and possibly other marsupials with vincristine susceptible cancers, these findings strongly suggest that vincristine will not be effective in the treatment of DFTD.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Veterinary Science, University of Sydney, Sydney, New South Wales, Australia. david.phalen@sydney.edu.au

ABSTRACT
Tasmanian Devil Facial Tumor Disease (DFTD) is a transmissible cancer threatening to cause the extinction of Tasmanian Devils in the wild. The aim of this study was to determine the susceptibility of the DFTD to vincristine. Escalating dosage rates of vincristine (0.05 to 0.136 mg/kg) were given to Tasmanian devils in the early stages of DFTD (n = 8). None of these dosage rates impacted the outcome of the disease. A dosage rate of 0.105 mg/kg, a rate significantly higher than that given in humans or domestic animals, was found to the highest dosage rate that could be administered safely. Signs of toxicity included anorexia, vomiting, diarrhea and neutropenia. Pharmacokinetic studies showed that, as with other species, there was a rapid drop in blood concentration following a rapid intravenous infusion with a high volume of distribution (1.96 L/kg) and a relatively long elimination half life (11 h). Plasma clearance (1.8 ml/min/kg) was slower in the Tasmanian devil than in humans, suggesting that pharmacodynamics and not pharmacokinetics explain the Tasmanian devil's ability to tolerate high dosage rates of vincristine. While providing base-line data for the use of vincristine in Tasmanian devils and possibly other marsupials with vincristine susceptible cancers, these findings strongly suggest that vincristine will not be effective in the treatment of DFTD.

Show MeSH
Related in: MedlinePlus