Extensive and saturable accumulation of paclitaxel by the human platelet

Cancer Chemother Pharmacol. 1995;36(1):41-4. doi: 10.1007/BF00685730.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Binding Sites
  • Blood Platelets / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paclitaxel / blood
  • Paclitaxel / pharmacokinetics*

Substances

  • Paclitaxel