title: Utility of a population pharmacokinetic meta analysis during the approval process of teduglutide for the treatment of short bowel syndrome.
abstract: OBJECTIVE
  Teduglutide is a recombinant analogue of human glucagonlike peptide-2 (GLP-2) that was recently approved by the US and European regulatory agencies FDA and EMA for the treatment of short bowel syndrome (SBS). The objectives of this work were, firstly, to develop a population pharmacokinetic (popPK) model based on the available PK data of the entire clinical development program and, secondly, to utilize the model for the justification of the proposed dosing regimen. The exploratory analysis was based on a previously established structural PK model and focused primarily on the investigation of covariate effects.
  
  
  RESULTS
  The plasma concentrationtime profiles of teduglutide after subcutaneous application were adequately described by a 1-compartment model with first order absorption and elimination. The area under the curve (AUC) was lower for male subjects, for subjects with higher creatinine clearance, for overweight subjects, and for SBS patients. However, except for subjects with severe renal impairment no clinically relevant effects on AUC were identified.
  
  
  CONCLUSIONS
  Our model-based analysis supports the approved dose adjustment for SBS patients with and without renal impairments maintaining the exposure in a value range with acceptable variance for the target population.
authors: Stefan
authors: S
authors: Roepcke
authors: Ruediger
authors: R
authors: Nave
authors: Jane
authors: J
authors: Cyran
authors: Nele
authors: N
authors: Plock
authors: Gezim
authors: G
authors: Lahu
authors: Axel
authors: A
authors: Facius
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017277:Drug Approval; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D008954:Models, Biological; D010455:Peptides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000378:metabolism; D012778:Short Bowel Syndrome / Q000188:drug therapy*
chemical_list: D010455:Peptides; C494910:teduglutide