In Vitro and in Vivo Studies on Plasma-to-Blood Ratio of Paclitaxel in Human, Rabbit and Rat Blood Fractions

Abstract

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.

A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, andIn VivoAntitumor Efficacy and Safety

“…PTX was measured in plasma and blood according to a previous report [22]. Briefly, an aliquot of 100  μ l plasma (or blood), 50  μ l docetaxel solution (10  μ g/mL, as an internal standard), and 2.5 mL acetonitrile were mixed using a vortex mixer for 30 s. The mixture was centrifuged at 3000 g for 10 min, then 2.0 mL supernatant was collected, and dried under a gentle stream of nitrogen gas at 50°C in a water bath.…”

Antiangiogenic Activity of Sterically Stabilized Liposomes Containing Paclitaxel (SSL-PTX): In Vitro and In Vivo

“…The concentration of paclitaxel in SSL-PTX was determined by an HPLC method (26) by Waters HPLC system consisting of a 1525 pump and a 2487 ultraviolet detector (Waters Co. Inc., Westerville, OH, USA). Mobile phase consisted of methanol-water-tetrahydrofuran (67.5:30:2.5, v/v/v) and was delivered at a flow rate of 1 ml/min.…”

Pharmacokinetics, tissue distribution and anti-tumour efficacy of paclitaxel delivered by polyvinylpyrrolidone solid dispersion

“…This is due to paclitaxel being encapsulated into CrEL micelles and these micelles mainly exist in the water phase of the plasma. Our previous results showed that PVP, unlike CrEL, did not affect the distribution of paclitaxel in blood [13] . Many CrEL‐free paclitaxel formulations have been evaluated by comparing systemic exposure of paclitaxel in plasma with Taxol.…”

“…It has been reported that CrEL influences the distribution of paclitaxel in the blood of humans [12] and experimental animals [13] . By trapping paclitaxel in CrEL micelles, CrEL reduces the free paclitaxel fraction and changes the pharmacokinetic profile of paclitaxel [12] .…”