title: Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose Phase-I safety trial in spinal cord-injured and able-bodied volunteers.
abstract: METHODS
  Single centre, single ascending dose study.
  
  
  OBJECTIVE
  To compare the pharmacokinetics and assess the safety of capromorelin, a compound that has potential to treat constipation following spinal cord injury (SCI), in groups of able-bodied and SCI volunteers.
  
  
  METHODS
  Local population from Victoria, Australia.
  
  
  METHODS
  Following initial screening and baseline blood collections, participants received ascending oral doses (20, 50 and then 100 mg at least 1-week apart) of capromorelin after pre-dose blood collection, followed by blood collections over the following 12 h for pharmacokinetic analysis and 1-week and 4-week follow-up blood collections for safety evaluations. Blood pressure and heart rate were monitored.
  
  
  RESULTS
  No serious adverse events were recorded following any dose in either the able-bodied group or the SCI group. There were no abnormal blood pressure or heart rate changes. Minor adverse events resolved quickly without the need for treatment. Pharmacokinetic behaviour was broadly similar between groups, with both exhibiting dose-dependent increases in Cmax and AUC0-∞. The SCI participants showed greater variance in pharmacokinetic parameters and had a slightly delayed Tmax and half-life.
  
  
  CONCLUSIONS
  Capromorelin at the doses tested was safe and well tolerated in both SCI and able-bodied participants and also showed similar pharmacokinetics with dose-dependent increases in concentration and drug exposure.
authors.affiliation: 1] Clinical Pharmacology and Therapeutics, Austin Health, Heidelberg, Victoria, Australia [2] Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: A G
authors.initials: AG
authors.lastname: Ellis
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: P T
authors.initials: PT
authors.lastname: Zeglinski
authors.affiliation: 1] Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia [2] Spinal Research Institute, Royal Talbot Rehabilitation Centre, Victoria, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Brown
authors.affiliation: 1] Clinical Pharmacology and Therapeutics, Austin Health, Heidelberg, Victoria, Australia [2] Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: A G
authors.initials: AG
authors.lastname: Frauman
authors.affiliation: Spinal Research Institute, Royal Talbot Rehabilitation Centre, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Millard
authors.affiliation: 1] Spinal Research Institute, Royal Talbot Rehabilitation Centre, Victoria, Australia [2] Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: J B
authors.initials: JB
authors.lastname: Furness
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001337:Autonomic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D054439:Ghrelin / Q000819:agonists; D006207:Half-Life; D006801:Humans; D008297:Male; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011720:Pyrazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D013119:Spinal Cord Injuries / Q000097:blood* / Q000188:drug therapy*; D014739:Victoria
chemical_list: D001337:Autonomic Agents; C433143:CP 424391; D054439:Ghrelin; D010880:Piperidines; D011720:Pyrazoles