title: The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying.
abstract: Here we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis.
  
  
  
  In a randomized, double-blind, placebo-controlled, incomplete block, three-period, two-centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg). Gastric emptying ((13) C-octanoic acid breath test), pharmacokinetics and safety were primary outcomes.
  
  
  
  Nine of the 10 patients enrolled completed the study. Gastric half-emptying time decreased by -95 min (95% CI: -156.8, -34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P < 0.05), representing a 65% improvement. A decrease of the gastric half-emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure-response relationship was demonstrated across all doses. The effects of camicinal on gastric half-emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose-proportional pharmacokinetic characteristics and a clear exposure-response relationship with gastric emptying.
  
  
  
  Camicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.
authors.affiliation: Uppsala University, Uppsala, Sweden.
authors.forename: Per M
authors.initials: PM
authors.lastname: Hellström
authors.affiliation: University of Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Lakshmi Vasist
authors.initials: LV
authors.lastname: Johnson
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Hacquoil
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Barton
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: Duncan B
authors.initials: DB
authors.lastname: Richards
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Alpers
authors.affiliation: Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Sanger
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Dukes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D006801:Humans; D008875:Middle Aged; D009037:Motilin / Q000819:agonists* / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; C541863:N-(3-fluorophenyl)-1-((4-(((3S)-3-methyl-1-piperazinyl)methyl)phenyl)acetyl)-4-piperidinamine; D010879:Piperazines; D010880:Piperidines; D009037:Motilin