Abstract
BACKGROUND AND OBJECTIVES: Vedolizumab is a humanized monoclonal antibody, indicated for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), that specifically binds to the α4β7 integrin. The aim of this study was to assess the pharmacokinetics, safety, and tolerability of vedolizumab following a single intravenous (IV) infusion in healthy adult Chinese subjects. METHODS: Sixteen participants received a single IV infusion of vedolizumab (300 mg). Blood samples were collected to measure vedolizumab serum concentrations. The safety of all subjects was monitored. RESULTS: The pharmacokinetic analysis showed that vedolizumab reached the maximum observed serum concentration (C(max)) at approximately 1.32 hours. The mean C(max) and area under the concentration-time curve from time 0 to time of the last quantifiable concentration (AUC(0-t)) and to infinity (AUC(0-∞)) were 137.25 µg/mL, 2360 days·µg/mL, and 2395 days·µg/mL, respectively. The elimination of vedolizumab was relatively slow, with a mean terminal disposition phase half-life elimination (t(1/2)) of 20.23 days. Six subjects were positive for anti-vedolizumab antibodies (AVAs) on day 106 and day 127. Finally, 4 out of 16 subjects (25.0%) had treatment-emergent adverse events (TEAEs), all of which were upper respiratory tract infections. CONCLUSION: Vedolizumab was well tolerated in healthy Chinese subjects when administered as a single-dose IV 300 mg infusion. In this study, the rate of AVA positivity was 37.5%, which occurred near the end of the study; no significant differences in pharmacokinetic profiles were observed between the AVA-positive and AVA-negative groups. CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn : CTR20171528.