AUTHOR=Li Qingmei , Zhang Hong , Zhu Xiaoxue , Liu Chengjiao , Wu Min , Li Cuiyun , Li Xiaojiao , Gao Lei , Ding Yanhua 

TITLE=Tolerance, Variability and Pharmacokinetics of Albumin-Bound Paclitaxel in Chinese Breast Cancer Patients

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.01372

DOI=10.3389/fphar.2018.01372

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of albumin-bound paclitaxel (QL, HR, ZDTQ) among Chinese breast cancer patients.</p><p><bold>Methods:</bold> Three randomized, open-label, two-period crossover bioequivalence studies were conducted with albumin-bound paclitaxel. Each subject received a single dose of 260 mg/m<sup>2</sup> albumin-bound paclitaxel [sponsor 1 (QL, light food), sponsor 2 (HR, fasting), sponsor 3 (ZDTQ, light food); test] or Abraxane® (reference) and was monitored for 72 h. Serum concentrations of total paclitaxel and unbound paclitaxel were measured using liquid chromatography/mass spectrometry (LC/MS), and appropriate pharmacokinetic parameters were determined by non-compartmental methods. Safety assessments included adverse events, hematology and biochemistry tests.</p><p><bold>Results:</bold> The bioequivalence analyses of the QL, HR, and ZDTQ products included 24, 23, and 24 patients, respectively. The mean t<sub>1/2</sub> was 20.61–27.31 h for total paclitaxel. Food intake did not affect the pharmacokinetics of paclitaxel. From the comparison of total paclitaxel and unbound paclitaxel, the 90% confidence intervals (CIs) for the ratios of C<sub>max</sub>, AUC<sub>0−t</sub>, and AUC<sub>0−∞</sub> were within 80.00–125.00%. The intra-subject variability ranged from 6.4–11% to 9.85–15.87% for total paclitaxel and unbound paclitaxel, respectively. Almost all subjects in the test and Abraxane® (reference) groups experienced mild or moderate adverse events. No fatal AEs or study drug injection site reactions related to these drugs were observed.</p><p><bold>Conclusion:</bold> Albumin-bound paclitaxel (QL, HR or ZDTQ; test products) showed bioequivalence to Abraxane® (reference) with lower intra-subject variability, which was less than 16% in all cases, and was well-tolerated in Chinese breast cancer patients. Twenty-two patients are enough for an albumin-bound paclitaxel bioequivalence study.</p>