Tubulin as a major determinant of tissue distribution of vincristine.
The tissue distribution of vincristine was correlated with the tubulin content in different mouse tissues. The concentration of tubulin in the mouse tissues was determined by estimation of the tissue binding capacities for colchicine. Significant differences in the tubulin concentration were observed among the tissues. The comparison of the apparent tissue-to-plasma partition coefficients (KPapp) of vincristine (taken from the literature) with the tubulin concentration (expressed by the binding capacities for colchicine) showed a good correlation. These results suggest that the in vivo distribution of vincristine is predicted by the tissue tubulin concentration.
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
K
K
Wierzba
Y
Y
Sugiyama
K
K
Okudaira
T
T
Iga
M
M
Hanano
D000818:Animals; D003078:Colchicine / Q000378:metabolism; D008297:Male; D051379:Mice; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution; D014404:Tubulin / Q000502:physiology*; D014750:Vincristine / Q000493:pharmacokinetics*
D014404:Tubulin; D014750:Vincristine; D003078:Colchicine