Bristol-Myers Squibb Research and Development, Princeton, New Jersey, USA.
Br J Clin Pharmacol. 2013 Mar;75(3):763-8. doi: 10.1111/j.1365-2125.2012.04391.x.
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).
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.
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.
Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability.
采用同时静脉内¹⁴C-微剂量/治疗口服给药（i.v.微+口服治疗），确定沙格列汀和达格列净的绝对口服生物利用度（F(p.o.)）。
在健康受试者中（分别为 n = 7 和 8），同时给予单次静脉内微剂量和未标记的口服治疗剂量后，确定沙格列汀和达格列净的 F(p.o.)值。采用加速器质谱法和液相色谱-串联质谱法分别定量标记和未标记药物。
沙格列汀和达格列净的几何均数点估计值（90%置信区间）F(p.o.)值分别为 50%（48, 53%）和 78%（73, 83%）。i.v.微与口服治疗具有相似的药代动力学特征。
同时进行 i.v.微+口服治疗给药是评估人体绝对生物利用度的有价值工具。
