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Clinical pharmacokinetics and effects of vincristine sulfate in dogs with transmissible venereal tumor (TVT).

Hantrakul S, Klangkaew N, Kunakornsawat S, Tansatit T, Poapolathep A, Kumagai S, Poapolathep S - J. Vet. Med. Sci. (2014)

Bottom Line: The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model.The volume of distribution, distribution half-life, elimination half-life and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min and 0.010 ± 0.001 l/min/kg, respectively.In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University Bangkok 10900, Thailand.

ABSTRACT
This study was conducted to evaluate the pharmacokinetic characteristics of vincristine and their correlation with its clinical effects in dogs with transmissible venereal tumor (TVT). Dogs with TVT were intravenously administered vincristine sulfate at a dose of 0.7 mg/m(2) of body surface area. Blood samples were collected starting from 5 min to 48 hr after drug administration. The plasma concentration of vincristine was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model. The volume of distribution, distribution half-life, elimination half-life and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min and 0.010 ± 0.001 l/min/kg, respectively. Tumor regression was determined at weekly interval by a physical examination and histopathological analysis. In our study, three to eight administrations of vincristine at a dose of 0.7 mg/m(2) were able to induce a complete tumor regression without any evidence of gross lesion of disease. Therefore, this investigation provides the pharmacokinetic characteristics of vincristine in dogs with TVT, which may be used as an integration tool to gain a better understanding of the disposition properties of the drug and the correlation of these properties with the drug's clinical effects. In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.

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Time profile of vincristine plasma concentration after its intravenous administrationto dogs with TVT at a dose of 0.7 mg/m2. The values represent the means ±SD (n=6).
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fig_001: Time profile of vincristine plasma concentration after its intravenous administrationto dogs with TVT at a dose of 0.7 mg/m2. The values represent the means ±SD (n=6).

Mentions: Pharmacokinetic analysis: The level of vincristine sulfate in plasma wasdetectable up to 120 min after drug administration. Figure 1Fig. 1.


Clinical pharmacokinetics and effects of vincristine sulfate in dogs with transmissible venereal tumor (TVT).

Hantrakul S, Klangkaew N, Kunakornsawat S, Tansatit T, Poapolathep A, Kumagai S, Poapolathep S - J. Vet. Med. Sci. (2014)

Time profile of vincristine plasma concentration after its intravenous administrationto dogs with TVT at a dose of 0.7 mg/m2. The values represent the means ±SD (n=6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300367&req=5

fig_001: Time profile of vincristine plasma concentration after its intravenous administrationto dogs with TVT at a dose of 0.7 mg/m2. The values represent the means ±SD (n=6).
Mentions: Pharmacokinetic analysis: The level of vincristine sulfate in plasma wasdetectable up to 120 min after drug administration. Figure 1Fig. 1.

Bottom Line: The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model.The volume of distribution, distribution half-life, elimination half-life and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min and 0.010 ± 0.001 l/min/kg, respectively.In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University Bangkok 10900, Thailand.

ABSTRACT
This study was conducted to evaluate the pharmacokinetic characteristics of vincristine and their correlation with its clinical effects in dogs with transmissible venereal tumor (TVT). Dogs with TVT were intravenously administered vincristine sulfate at a dose of 0.7 mg/m(2) of body surface area. Blood samples were collected starting from 5 min to 48 hr after drug administration. The plasma concentration of vincristine was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model. The volume of distribution, distribution half-life, elimination half-life and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min and 0.010 ± 0.001 l/min/kg, respectively. Tumor regression was determined at weekly interval by a physical examination and histopathological analysis. In our study, three to eight administrations of vincristine at a dose of 0.7 mg/m(2) were able to induce a complete tumor regression without any evidence of gross lesion of disease. Therefore, this investigation provides the pharmacokinetic characteristics of vincristine in dogs with TVT, which may be used as an integration tool to gain a better understanding of the disposition properties of the drug and the correlation of these properties with the drug's clinical effects. In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.

Show MeSH
Related in: MedlinePlus