title: Simultaneous oral therapeutic and intravenous ¹⁴C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin.
abstract: OBJECTIVE
  To determine the absolute oral bioavailability (F(p.o.) ) of saxagliptin and dapagliflozin using simultaneous intravenous ¹⁴C-microdose/therapeutic oral dosing (i.v.micro + oraltherap).
  
  
  METHODS
  The F(p.o.) values of saxagliptin and dapagliflozin were determined in healthy subjects (n = 7 and 8, respectively) following the concomitant administration of single i.v. micro doses with unlabelled oraltherap doses. Accelerator mass spectrometry and liquid chromatography-tandem mass spectrometry were used to quantify the labelled and unlabelled drug, respectively.
  
  
  RESULTS
  The geometric mean point estimates (90% confidence interval) F(p.o) . values for saxagliptin and dapagliflozin were 50% (48, 53%) and 78% (73, 83%), respectively. The i.v.micro had similar pharmacokinetics to oraltherap.
  
  
  CONCLUSIONS
  Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability.
authors: Bristol-Myers Squibb Research and Development, Princeton, New Jersey, USA. david.boulton@bms.com
authors: David W
authors: DW
authors: Boulton
authors: Sreeneeranj
authors: S
authors: Kasichayanula
authors: Chi Fung Anther
authors: CF
authors: Keung
authors: Mark E
authors: ME
authors: Arnold
authors: Lisa J
authors: LJ
authors: Christopher
authors: Xiaohui Sophia
authors: XS
authors: Xu
authors: Frank
authors: F
authors: Lacreta
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001559:Benzhydryl Compounds; D001682:Biological Availability; D002853:Chromatography, Liquid; D004151:Dipeptides / Q000493:pharmacokinetics*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D051247:Sodium-Glucose Transport Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D044465:White People; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D051247:Sodium-Glucose Transport Proteins; C529054:dapagliflozin; C502994:saxagliptin; D000218:Adamantane