title: Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake.
abstract: OBJECTIVE
  The aim of the study was to better understand blonanserin population pharmacokinetic (PK) characteristics in Chinese healthy subjects.
  
  
  METHODS
  Data from two studies with 50 subjects were analyzed to investigate the population PK characteristics of blonanserin at single dose (4, 8, and 12 mg) under fasting, multidose (4 mg bid or 8 mg qd for 7 days) and under food intake condition (single dose, 8 mg). Blonanserin plasma concentrations were detected using the high performance liquid chromatography tandem mass spectrometry (LC/MS/MS). A nonlinear mixed-effects model was developed to describe the blonanserin concentration-time profiles.
  
  
  RESULTS
  A two compartment model with first-order absorption was built to describe the time-course of blonanserin. The population-predicted system apparent clearance (CL/F), volume of apparent distribution in center (V(1)/F), and the first-order absorption rate constant (Ka) of blonanserin under fasting was 1230 L/h, 9500 L, and 3.02 h(-1), respectively. Food intake decreased Ka of blonanserin to 0.78 h(-1). The relative bioavailability between fasting and food intake estimated by the final model was 55%. No clinically significant safety issues were identified.
  
  
  CONCLUSIONS
  This is the first study assessing the PK profile of blonanserin with population PKs method. The results can be used for simulation in further clinical trial and optimize individual dosage regimens using a Bayesian methodology in patients.
authors: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, Guangzhou, China. wenyuguande@163.com
authors: Yu-Guan
authors: YG
authors: Wen
authors: De-Wei
authors: DW
authors: Shang
authors: He-Zhi
authors: HZ
authors: Xie
authors: Xi-Pei
authors: XP
authors: Wang
authors: Xiao-Jia
authors: XJ
authors: Ni
authors: Ming
authors: M
authors: Zhang
authors: Wei
authors: W
authors: Lu
authors: Chang
authors: C
authors: Qiu
authors: Xia
authors: X
authors: Liu
authors: Fang-Fang
authors: FF
authors: Li
authors: Xuan
authors: X
authors: Li
authors: Fu-Tian
authors: FT
authors: Luo
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D044466:Asian People; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D010880:Piperidines / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D010879:Piperazines; D010880:Piperidines; C079310:blonanserin