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Keywords:

  • absolute bioavailability;
  • accelerator mass spectrometry (AMS);
  • dapagliflozin;
  • intravenous 14C-microdose;
  • microtracer;
  • saxagliptin

Aim

To determine the absolute oral bioavailability (Fp.o.) of saxagliptin and dapagliflozin using simultaneous intravenous 14C-microdose/therapeutic oral dosing (i.v.micro + oraltherap).

Methods

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.

Results

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.

Conclusions

Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability.