Pharmacokinetic profile of paclitaxel in the plasma, lung, and diaphragm following intravenous or intrapleural administration in rats

Abstract

Background

The optimal chemotherapy route for non-small cell lung cancers involving the phrenic nerve and diaphragm is unclear. The pharmacokinetic properties of paclitaxel following intravenous (IV) or intrapleural (IP) administration were analyzed in the plasma, lung, and diaphragm in a rat model. The purpose of this study was to determine whether IP injection increased paclitaxel concentration in the diaphragm.

Methods

Paclitaxel was administered by IV or IP to male Sprague-Dawley rats. The concentration of drug in the plasma, lung, and diaphragm was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters area under the curve (AUC), mean residence time (MRT), peak plasma concentration (C _max), and half-life (t _1/2) were analyzed.

Results

Paclitaxel concentration in the plasma, lung, and diaphragm decreased quickly following IV administration. However, after IP injection, paclitaxel reached a high concentration in the plasma, lung, and diaphragm that declined gradually. Significant differences in all parameters, except C _max in the lung, were observed between the two routes of administration (all P < 0.05). Plasma exposure to paclitaxel IP was 41.1% of that observed after IV in the first 24 hours ( P < 0.05). IP also significantly increased exposure of paclitaxel in comparison with IV administration to 267.3% and 905.7% of IV administration in the lung and diaphragm, respectively ( P < 0.05).

Conclusion

These results suggest that IP administration may reduce systemic distribution of paclitaxel and increase the concentration in the lung and diaphragm. This could increase therapeutic efficacy by increasing the available drug and reduce systemic toxicity.