Md. Wild et al., EXTENSIVE AND SATURABLE ACCUMULATION OF PACLITAXEL BY THE HUMAN PLATELET, Cancer chemotherapy and pharmacology, 36(1), 1995, pp. 41-44
Little is known about the cellular distribution of paclitaxel in human
s. In the present study we examined the distribution of [H-3]-paclitax
el in human blood. When 1 mu M paclitaxel was incubated with fresh blo
od at 37 degrees C, the platelet/plasma concentration ratio was 240 +/
- 17 (mean +/- SEM), whereas the red blood cell (RBC)/plasma concentra
tion ratio was only 0.59 +/- 0.05. In kinetics experiments using plate
let-rich plasma, we observed that the platelet accumulation of paclita
xel was highly temperature- and concentration-dependent. Scatchard ana
lysis of the 37 degrees C uptake data demonstrated a dissociation cons
tant (K-app) of 0.80 +/- 0.10 mu M and a maximal binding capacity of 6
72 +/- 102 pmol/10(9) platelets. It is proposed that the platelet accu
mulation of paclitaxel reflects binding to microtubules and may serve
as a useful model for binding to less accessible cellular sites.