In vitro and in vivo studies on plasma-to-blood ratio of paclitaxel in human, rabbit and rat blood fractions.
Many pharmacokinetic studies of paclitaxel formulations with or without Cremophor (CrEL) have been performed on experimental animals. However, limited studies describe the different pharmacokinetic behaviors of paclitaxel in animals. The different distribution of drug in blood fractions may have great effect on its pharmacokinetic behaviors. Our present study was designed to study the characteristics of paclitaxel distribution in human, rabbit and rat blood, by measuring plasma-to-blood ratio (PBR) of paclitaxel in vitro and in vivo, and analyzing the results of equilibrium dialysis of paclitaxel with erythrocyte, plasma and hemoglobin. It was demonstrated that the paclitaxel PBR values in rat, unlike those in rabbit, are most significantly different from those in human, which may be due to distinct affinity of paclitaxel to blood fractions among different species. The effect of CrEL on increasing paclitaxel plasma concentration and in vitro & in vivo correlation in animal PBR values were observed. The findings in this study are of significance in the evaluation of the newly developed formulations of paclitaxel.
Liu
Xiang-Rui
XR
Department of Pharmaceutics, Peking University, Beijing, China.
Wu
Ke-Chun
KC
Huang
Yue
Y
Sun
Jia-Bei
JB
Ke
Xi-Yu
XY
Wang
Jian-Cheng
JC
Lu
Wan-Liang
WL
Zhang
Xuan
X
Zhang
Qiang
Q
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D003956:Dialysis; D004912:Erythrocytes / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D017239:Paclitaxel / Q000097:blood*; D010949:Plasma / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D000972:Antineoplastic Agents, Phytogenic; D006454:Hemoglobins; D017239:Paclitaxel