title: Effect of varying degrees of renal impairment on the pharmacokinetics and tolerability of taspoglutide.
abstract: To evaluate single-dose pharmacokinetics and tolerability of taspoglutide in people with varying degrees of renal impairment and matched healthy participants.
  
  
  
  Participants in the present study were people with mild renal impairment (n = 10), moderate impairment (n = 10), severe impairment (n = 9), and a matched healthy control group (n = 10). Participants received a single subcutaneous injection of taspoglutide (10 mg) on day 1. Plasma and urine drug concentration, antibody formation, vital signs, ECGs and routine laboratory variables were measured frequently and adverse events (AEs) were monitored for 9 weeks.
  
  
  
  Taspoglutide exposure was higher among participants with moderate and severe renal impairment compared with participants with normal renal function. Mean AUClastwas 13% and 38% higher in participants with moderate and severe renal impairment, respectively compared with participants with normal renal function. Likewise, mean peak plasma concentration (Cmax) was 57% and 93% higher in participants with moderate and severe renal function impairment, respectively, compared with participants with normal renal function. Linear regression analyses showed a statistically significant inverse relationship between taspoglutide exposure parameters (AUC and Cmax) and creatinine clearance. Higher incidences of gastrointestinal (GI) AEs were reported in participants with severe renal impairment.
  
  
  
  Renal impairment altered the pharmacokinetics of taspoglutide. The degree of renal impairment was associated with an increased exposure to taspoglutide and an increased risk of GI AEs.
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Mylène
authors.initials: M
authors.lastname: Giraudon
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sturm
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lambert
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Niggli
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: Jochen
authors.initials: J
authors.lastname: Brumm
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Mangold
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000187:drug effects; D003404:Creatinine / Q000032:analysis; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007677:Kidney Function Tests; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D010455:Peptides / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism*
chemical_list: D010455:Peptides; C541736:taspoglutide; D003404:Creatinine
keywords: 
  GLP-1 agonist; incretin; pharmacokinetics; renal function; taspoglutide; tolerability