EXTENSIVE AND SATURABLE ACCUMULATION OF PACLITAXEL BY THE HUMAN PLATELET

Citation
Md. Wild et al., EXTENSIVE AND SATURABLE ACCUMULATION OF PACLITAXEL BY THE HUMAN PLATELET, Cancer chemotherapy and pharmacology, 36(1), 1995, pp. 41-44
Citations number
19
Categorie Soggetti
Pharmacology & Pharmacy",Oncology
ISSN journal
03445704
Volume
36
Issue
1
Year of publication
1995
Pages
41 - 44
Database
ISI
SICI code
0344-5704(1995)36:1<41:EASAOP>2.0.ZU;2-K
Abstract
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.