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, AUC0-96h values in pleural fluid and plasma were 17831 ± 6439 μgh/mL and 778 ± 328 μgh/mL, respectively, and Tmax values were initial time and 6.67 h after administration and the corresponding Cmax values were 558 ± 44 μg/mL and 12.89 ± 6.86 μg/mL, respectively. The T1/2 IP, CLIP and VdIP values in pleural fluid were 76 ± 48 h, 0.005 ± 0.002 L/hm2 and 0.53 ± 0.23 L/m2, respectively. The T1/2,pla, CLpla, and Vdpla values in plasma were 68.34 ± 56.74 h, 0.184 ± 0.080 L/hm2, and 17.53 ± 16.57 L/m2, 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.