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 AE 6439 mg h/mL and 778 AE 328 mg h/mL, respectively, and T max values were initial time and 6.67 h after administration and the corresponding C max values were 558 AE 44 mg/mL and 12.89 AE 6.86 mg/mL, respectively. The T 1/2,IP , CL IP and Vd IP values in pleural fluid were 76 AE 48 h, 0.005 AE 0.002 L/h m 2 and 0.53 AE 0.23 L/m 2 , respectively. The T 1/2,pla , CL pla , and Vd pla values in plasma were 68.34 AE 56.74 h, 0.184 AE 0.080 L/h m 2 , and 17.53 AE 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.