title: Pharmacokinetics of teduglutide in subjects with renal impairment.
abstract: OBJECTIVE
  Teduglutide is a recombinant analogue of human glucagon-like peptide-2 that has recently been approved for the treatment of short bowel syndrome in adults. This study was designed to study the influence of renal function and age on teduglutide pharmacokinetics.
  
  
  METHODS
  This was an open-label study with six parallel groups (6 subjects each). Three groups with renal impairment (moderate, severe and end-stage renal disease) were compared to healthy subjects with normal renal function, which were matched to the renal-impaired subjects with respect to demographics. At least two elderly subjects (≥65 years) were enrolled per group. A single dose of 10 mg teduglutide was subcutaneously administered to each subject. Teduglutide plasma concentrations were measured using a validated liquid chromatography method with tandem mass spectrometric detection, and the primary pharmacokinetic variables (AUCinf and Cmax) were calculated.
  
  
  RESULTS
  Area under the concentration versus time curve extrapolated to infinity (AUCinf) and maximum plasma concentration (Cmax) of teduglutide in subjects with end-stage renal disease were approximately 2.59- and 2.08-fold higher, respectively, than those of healthy subjects. The AUCinf and Cmax were also slightly higher in subjects with moderate and severe renal impairment. Comparison of healthy subjects aged <65 years with healthy elderly subjects revealed very similar pharmacokinetics in both subgroups.
  
  
  CONCLUSIONS
  In our study population, the primary pharmacokinetic parameters of teduglutide increased with increased severity of renal impairment. These results suggest that the daily dose of teduglutide should be reduced by 50 % in patients with moderate and severe renal impairment and end-stage disease. We found no effect of age on the pharmacokinetics of teduglutide in healthy subjects. The treatment was well tolerated, and there were no safety concerns.
authors.affiliation: Nycomed GmbH, Nycomed: A Takeda Company, Constance, Germany. ruediger.nave@takeda.com
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Nave
authors.forename: Atef
authors.initials: A
authors.lastname: Halabi
authors.forename: Rolf
authors.initials: R
authors.lastname: Herzog
authors.forename: Peter
authors.initials: P
authors.lastname: Schaffer
authors.forename: Jörg
authors.initials: J
authors.lastname: Diefenbach
authors.forename: Stephan
authors.initials: S
authors.lastname: Krause
authors.forename: Peter
authors.initials: P
authors.lastname: Berghöfer
authors.forename: Gezim
authors.initials: G
authors.lastname: Lahu
authors.forename: Manfred
authors.initials: M
authors.lastname: Hartmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000097:blood* / Q000175:diagnosis
chemical_list: D010455:Peptides; C494910:teduglutide