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(0-96 h) values in pleural fluid and plasma were 17831 ± 6439 µg h/mL and 778 ± 328 µg h/mL, respectively, and T(max) values were initial time and 6.67 h after administration and the corresponding C(max) values were 558 ± 44 µg/mL and 12.89 ± 6.86 µg/mL, respectively. The T(1/2,IP), CL(IP) 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), CL(pla), 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.
Wang
Xianhuo
X
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Zheng
Hao
H
Zhu
Zhengyan
Z
Wei
Yuquan
Y
Chen
Lijuan
L
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004333:Drug Administration Routes; D006801:Humans; D016014:Linear Models; D008081:Liposomes; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D035422:Pleural Cavity / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000188:drug therapy; D012680:Sensitivity and Specificity
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D017239:Paclitaxel