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Novel Application of the Two-Period Microtracer Approach to Determine Absolute Oral Bioavailability and Fraction Absorbed of Ertugliflozin
- Source :
- Clinical and Translational Science. 11:405-411
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Ertugliflozin, a sodium glucose cotransporter-2 inhibitor, is approved in the United States for treatment of type 2 diabetes mellitus. A novel two-period study design with 14 C microtracer dosing in each period was used to determine absolute oral bioavailability (F) and fraction absorbed (Fa ) of ertugliflozin. Eight healthy adult men received 100-μg i.v. 14 C-ertugliflozin (400 nCi) dose 1 h after a 15-mg oral unlabeled ertugliflozin dose (period 1), followed by 100 μg 14 C-ertugliflozin orally along with 15 mg oral unlabeled ertugliflozin (period 2). Unlabeled ertugliflozin plasma concentrations were determined using high-performance liquid-chromatography tandem mass spectrometry (HPLC-MS/MS). 14 C-ertugliflozin plasma concentrations were determined using HPLC-accelerator mass spectrometry (AMS) and 14 C urine concentrations were determined using AMS. F ((area under the curve (AUC)p.o. /14 C-AUCi.v. )*(14 C-Dosei.v. /Dosep.o. )) and Fa ((14 C_Total_Urinep.o. /14 C_Total_Urinei.v. )* (14 C-Dosei.v. /14 C-Dosep.o. )) were estimated. Estimates of F and Fa were 105% and 111%, respectively. Oral absorption of ertugliflozin was complete under fasted conditions and F was ∼100%. Ertugliflozin was well tolerated.
- Subjects :
- Chromatography
Chemistry
General Neuroscience
Sodium
Area under the curve
chemistry.chemical_element
Fraction (chemistry)
General Medicine
Absorption (skin)
Urine
Tandem mass spectrometry
Mass spectrometry
030226 pharmacology & pharmacy
General Biochemistry, Genetics and Molecular Biology
Bioavailability
03 medical and health sciences
0302 clinical medicine
030220 oncology & carcinogenesis
General Pharmacology, Toxicology and Pharmaceutics
Subjects
Details
- ISSN :
- 17528054
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Clinical and Translational Science
- Accession number :
- edsair.doi...........43daa919a2dc9a808114b7cd6503d3f6