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

被引：72

作者：

Boulton, David W. ^{[1
]}

Kasichayanula, Sreeneeranj ^{[1
]}

Keung, Chi Fung ^{[1
]}

Arnold, Mark E. ^{[1
]}

Christopher, Lisa J. ^{[1
]}

Xu, Xiaohui ^{[1
]}

LaCreta, Frank ^{[1
]}

机构：

[1] Bristol Myers Squibb Res & Dev, Princeton, NJ USA

来源：

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY | 2013年 / 75卷 / 03期

关键词：

absolute bioavailability; accelerator mass spectrometry (AMS); dapagliflozin; intravenous; 14C-microdose; microtracer; saxagliptin; POSITION STATEMENT; MASS-SPECTROMETRY; IN-VITRO; PHARMACOKINETICS; MICRODOSE; ANIMALS; PROFILE;

D O I：

10.1111/j.1365-2125.2012.04391.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：763 / 768

页数：6

共 22 条

[1]

[Anonymous], 2006, 109 M REC PROV ABS B

[2] American college of clinical pharmacology position statement on the use of microdosing in the drug development process [J].