Simultaneous oral therapeutic and intravenous 14C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin
Article first published online: 5 FEB 2013
© 2012 Bristol–Myers Squibb, Co.. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Special Issue: Nutraceuticals Themed Section
Volume 75, Issue 3, pages 763–768, March 2013
How to Cite
Boulton, D. W., Kasichayanula, S., Keung, C. F., Arnold, M. E., Christopher, L. J., Xu, X. and LaCreta, F. (2013), Simultaneous oral therapeutic and intravenous 14C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin. British Journal of Clinical Pharmacology, 75: 763–768. doi: 10.1111/j.1365-2125.2012.04391.x
- Issue published online: 5 FEB 2013
- Article first published online: 5 FEB 2013
- Accepted manuscript online: 24 JUL 2012 02:35AM EST
- Manuscript Accepted: 8 JUL 2012
- Manuscript Received: 3 JAN 2012
- absolute bioavailability;
- accelerator mass spectrometry (AMS);
- intravenous 14C-microdose;
To determine the absolute oral bioavailability (Fp.o.) of saxagliptin and dapagliflozin using simultaneous intravenous 14C-microdose/therapeutic oral dosing (i.v.micro + oraltherap).
The Fp.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.
The geometric mean point estimates (90% confidence interval) Fp.o. values for saxagliptin and dapagliflozin were 50% (48, 53%) and 78% (73, 83%), respectively. The i.v.micro had similar pharmacokinetics to oraltherap.
Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability.