Premium
Simultaneous oral therapeutic and intravenous 14 C‐microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin
Author(s) -
Boulton David W.,
Kasichayanula Sreeneeranj,
Keung Chi Fung Anther,
Arnold Mark E.,
Christopher Lisa J.,
Xu Xiaohui Sophia,
LaCreta Frank
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2012.04391.x
Subject(s) - saxagliptin , bioavailability , pharmacokinetics , dapagliflozin , microdose , pharmacology , dosing , chemistry , cmax , medicine , chromatography , diabetes mellitus , insulin , endocrinology , metformin , sitagliptin , type 2 diabetes
Aim To determine the absolute oral bioavailability ( F p.o. ) of saxagliptin and dapagliflozin using simultaneous intravenous 14 C‐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.