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/m2 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/m2
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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