Extensive and saturable accumulation of paclitaxel by the human platelet.
Little is known about the cellular distribution of paclitaxel in humans. In the present study we examined the distribution of [3H]-paclitaxel in human blood. When 1 microM paclitaxel was incubated with fresh blood at 37 degrees C, the platelet/plasma concentration ratio was 240 +/- 17 (mean +/- SEM), whereas the red blood cell (RBC)/plasma concentration ratio was only 0.59 +/- 0.05. In kinetics experiments using platelet-rich plasma, we observed that the platelet accumulation of paclitaxel was highly temperature- and concentration-dependent. Scatchard analysis of the 37 degrees C uptake data demonstrated a dissociation constant (Kapp) of 0.80 +/- 0.10 microM and a maximal binding capacity of 672 +/- 102 pmol/10(9) platelets. It is proposed that the platelet accumulation of paclitaxel reflects binding to microtubules and may serve as a useful model for binding to less accessible cellular sites.
Wild
M D
MD
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA.
Walle
U K
UK
Walle
T
T
D000328:Adult; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics*
D017239:Paclitaxel