title: Comparison of pharmacokinetics, pharmacodynamics, safety, and tolerability of the amyloid β monoclonal antibody solanezumab in Japanese and white patients with mild to moderate alzheimer disease.
abstract: OBJECTIVE
  Solanezumab is a humanized anti-amyloid β monoclonal antibody being developed as a passive immunization treatment to slow the progression of Alzheimer disease (AD). Pharmacokinetics (PK), pharmacodynamics, safety, and tolerability after a single dose of solanezumab were compared between Japanese and white patients with AD.
  
  
  METHODS
  Japanese and white patients with mild to moderate AD were enrolled in 2 separate studies. In each study, single doses of solanezumab at 0.5, 1.5, 4.0, and 10.0 mg/kg were administered by intravenous infusion. Plasma concentrations of solanezumab and amyloid β (Aβ) were measured. A safety assessment was conducted up to 112 days after a single-dose administration of solanezumab.
  
  
  RESULTS
  The PK profile was similar between the Japanese and the white patients with AD. In both the Japanese and the white patients, clearance and volume of distribution appeared similar across doses, suggesting that solanezumab exhibited dose-proportional PK within the studied dose range. A marked increase in plasma total Aβ was observed; both the magnitude and time to reach maximum concentration tended to increase with increasing doses of solanezumab. Administration of solanezumab was generally well-tolerated in both Japanese and white patients with AD.
  
  
  CONCLUSIONS
  When administered as a per-kilogram single dose of solanezumab, PK and pharmacodynamics (plasma total Aβ1-40 concentration) in the Japanese patients with AD were comparable with those in the white patients with AD. In addition, solanezumab was generally well tolerated in both Japanese and white patients at all dose levels.
authors: Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Sannomiya Plaza Bldg 7-1-5, Isogamidori, Chuo-ku, Kobe 651-0086, Japan. uenaka_kazunori@lilly.com
authors: Kazunori
authors: K
authors: Uenaka
authors: Masako
authors: M
authors: Nakano
authors: Brian A
authors: BA
authors: Willis
authors: Stuart
authors: S
authors: Friedrich
authors: Lisa
authors: L
authors: Ferguson-Sells
authors: Robert A
authors: RA
authors: Dean
authors: Ichiro
authors: I
authors: Ieiri
authors: Eric R
authors: ER
authors: Siemers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood* / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use*; D019540:Area Under Curve; D044466:Asian People; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D044465:White People
chemical_list: D016229:Amyloid beta-Peptides; D061067:Antibodies, Monoclonal, Humanized; D014150:Antipsychotic Agents; C550616:solanezumab