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.