title: Exploration of Antiemetics for Osteoporosis Therapy-Induced Nausea and Vomiting Using PET Molecular Imaging Analysis to Gastrointestinal Pharmacokinetics.
abstract: OBJECTIVE
  To select appropriate antiemetics relieving teriparatide-induced nausea and vomiting during osteoporosis treatment using PET molecular imaging and pharmacokinetic analysis.
  
  
  METHODS
  Rats were pretreated with subcutaneous teriparatide, followed by oral administration of antiemetics with different pharmacological effects. The pharmacokinetics of antiemetics were assessed by oral administration of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) under free moving conditions in vivo. The effect of teriparatide on the permeability of Caco-2 cell membranes to [(18)F]FDG was assessed in vitro. The effects of antiemetics on teriparatide-induced suppression of gastrointestinal motility in vivo was assayed by positron emission tomography (PET) using orally administered [(18)F]FDG.
  
  
  RESULTS
  Teriparatide delayed the time-radioactivity profile of [(18)F]FDG in blood and significantly reduced its absorption rate constant (k a ), determined from non-compartmental analysis, to 60% of control. In contrast, co-administration of granisetron or mosapride restored the time-radioactivity profile and k a of [(18)F]FDG to control levels. Teriparatide had no effect on Caco-2 membrane permeability to [(18)F]FDG. Pharmacokinetic PET imaging data analysis quantitatively showed the pharmacological effects of teriparatide-induced suppression of upper gastrointestinal motility and its restoration by granisetron and mosapride.
  
  
  CONCLUSIONS
  Teriparatide-induced abdominal discomfort might be attributed to GI motility, and PET imaging analysis is a useful tool to for the selection of appropriate antiemetics.
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. tshingaki@riken.jp.
authors: Tomotaka
authors: http://orcid.org/0000-0002-7046-2097
authors: T
authors: Shingaki
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors: Yumiko
authors: Y
authors: Katayama
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors: Takayoshi
authors: T
authors: Nakaoka
authors: RIKEN Center for Molecular Imaging Sciences, reorganized to RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, Japan.
authors: Tadayuki
authors: T
authors: Takashima
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors: Kayo
authors: K
authors: Onoe
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors: Takashi
authors: T
authors: Okauchi
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors: Emi
authors: E
authors: Hayashinaka
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors: Yasuhiro
authors: Y
authors: Wada
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors: Yilong
authors: Y
authors: Cui
authors: RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
authors: Yasuyoshi
authors: Y
authors: Watanabe
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D018938:Caco-2 Cells; D065569:Gastrointestinal Absorption / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000378:metabolism; D017829:Granisetron / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010024:Osteoporosis / Q000188:drug therapy; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000009:adverse effects*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000932:Antiemetics; D001549:Benzamides; D050071:Bone Density Conservation Agents; D017829:Granisetron; D009025:Morpholines; D019379:Teriparatide; C062720:mosapride
keywords: antiemetics; gastrointestinal motility; osteoporosis; positron emission tomography (PET); teriparatide