title: The pharmacokinetic and safety profiles of blonanserin in healthy Chinese volunteers after single fasting doses and single and multiple postprandial doses.
abstract: OBJECTIVE
  Blonanserin is a novel atypical antipsychotic drug acting as a mixed serotonin 5-HT2A and dopamine D2 receptor antagonist. This study investigated the pharmacokinetics and safety of blonanserin in healthy Chinese males.
  
  
  METHODS
  This was an open-label trial with two parts. Twenty-four subjects were enrolled in part A to receive a single fasting dose of 4 or 8 mg blonanserin (each n = 12); part B recruited 12 subjects and administered single and sequentially twice-daily multiple postprandial doses of blonanserin 2 mg for 9 days. Serial blood samples were taken for the bioassay of plasma blonanserin and its four metabolites during both sub-studies. Safety was assessed, including repeat measurements of fasting serum prolactin, insulin, triglyceride and cholesterol.
  
  
  RESULTS
  Blonanserin was rapidly absorbed, accompanied with immediate plasma concentration elevation of the N-oxide form (M2) and gradual rises of the N-deethylated form (M1) and its downstream metabolites. The mean elimination half-life of blonanserin (7.7-11.9 h) was much longer than that of M2 (1.2-1.3 h) but shorter than that of M1 (26.4-31.4 h) after single fasting doses. After food intake, a single dose of 2 mg blonanserin resulted in total exposure and peak concentrations of blonanserin similar to those observed with a single fasting dose of blonanserin 4 mg. Moreover, the relationship of metabolite over parent compound ratio was different between M1 and M2 after single and multiple postprandial administrations (single dose vs multiple dose: M1, 0.33 vs 0.75; M2, 0.13 vs 0.067). Mild but transient increases of prolactin, insulin and triglyceride were observed.
  
  
  CONCLUSIONS
  The pharmacokinetics of blonanserin in Chinese subjects were similar to those observed in Japanese subjects. This study suggested that food intake not only increases the bioavailability of blonanserin but differently affects the pharmacokinetics of its metabolites as well. The drug was safe and well tolerated in healthy Chinese males.
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 41 Damucang Alley, Xicheng District, Beijing, 100032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Hongyun
authors.initials: H
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Wen
authors.initials: W
authors.lastname: Zhong
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Liu
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D044466:Asian People / Q000208:ethnology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000378:metabolism*; D005221:Fatigue / Q000139:chemically induced / Q000175:diagnosis; D005500:Follow-Up Studies; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010880:Piperidines / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D010879:Piperazines; D010880:Piperidines; C079310:blonanserin