Simultaneous oral therapeutic and intravenous ¹⁴C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin.

Aim: 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.
(© 2012 Bristol-Myers Squibb, Co.. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)