Clinical Pharmacokinetics of Paclitaxel Liposome with a New Route of Administration in Human Based on the Analysis with Ultra Performance Liquid Chromatography

We investigated the clinical pharmacokinetics of paclitaxel liposome with a new route of administration, which was intrapleural infusion, in nine advanced nonsmall-cell lung cancer (NSCLC) patients with malignant pleural effusions after a single administration. Paclitaxel concentrations were measured in pleural fluid and plasma using a simple and rapid ultra performance liquid chromatography (UPLC) method following intra- and inter-day validations. In subjects, AUC(0-96h) values in pleural fluid and plasma were 17831 +/- 6439 mu g h/mL and 778 +/- 328 mu g h/mL, respectively, and T-max values were initial time and 6.67h after administration and the corresponding C-max values were 558 +/- 44 mu g/mL and 12.89 +/- 6.86 mu g/mL, respectively. The T-1/2,T-IP, CLIP and Vd(IP) values in pleural fluid were 76 +/- 48 h, 0.005 +/- 0.002 L/h m(2) and 0.53 +/- 0.23 L/m(2), respectively. The T-1/2,(pla), CLpla, and Vd(pla) values in plasma were 68.34 +/- 56.74 h, 0.184 +/- 0.080 L/h m(2), and 17.53 +/- 16.57 L/m(2), respectively. However, some paclitaxel concentrations from several patients in plasma could not be detected at some designed time-points. Our results might offer new opportunities to design and determine individually appropriate therapeutic dosage regimens based on a pharmacokinetic profile. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4746-4752, 2010