Novel Application of the Two-Period Microtracer Approach to Determine Absolute Oral Bioavailability and Fraction Absorbed of Ertugliflozin.

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 C-14 microtracer dosing in each period was used to determine absolute oral bioavailability (F) and fraction absorbed (F-a) of ertugliflozin. Eight healthy adult men received 100-g i.v. C-14-ertugliflozin (400 nCi) dose 1 h after a 15-mg oral unlabeled ertugliflozin dose (period 1), followed by 100 g C-14-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). C-14-ertugliflozin plasma concentrations were determined using HPLC-accelerator mass spectrometry (AMS) and C-14 urine concentrations were determined using AMS. F ((area under the curve (AUC)(p.o.)/C-14-AUC(i.v.))*(C-14-Dose(i.v.)/Dose(p.o.))) and F-a ((C-14_Total_Urine(p.o.)/C-14_Total_Urine(i.v.))* (C-14-Dose(i.v.)/C-14-Dose(p.o.))) were estimated. Estimates of F and F-a were 105% and 111%, respectively. Oral absorption of ertugliflozin was complete under fasted conditions and F was approximate to 100%. Ertugliflozin was well tolerated.