Biotransformation and mass balance of the SGLT2 inhibitor empagliflozin in healthy volunteers. (June 2015) - Chen, Lin-Zhi
Abstract 1. The absorption, biotransformation and excretion of empagliflozin, an SGLT2 inhibitor, were evaluated in eight healthy subjects following a single 50 mg oral dose of empagliflozin containing ∼100 µCi [14C]-empagliflozin. 2. Radioactivity was rapidly absorbed, with plasma levels peaking 1 h post-dose. Total exposure was lower in blood versus plasma, consistent with moderate (28.6–36.8%) red blood cell partitioning. Protein binding was 80.3–86.2%. 3. Most of the radioactive dose was recovered in urine (54.4%) and faeces (41.1%). Unchanged empagliflozin was the most abundant drug-related component in plasma, representing 75.5–77.4% of plasma radioactivity and 79.6% plasma radioactivity AUC0–12 h. Unchanged empagliflozin was the most abundant drug-related component in urine and faeces, representing 43.5% (23.7% of dose) and 82.9% (34.1% of dose) of radioactivity in urine and faeces, respectively. Six metabolites were identified in plasma: three glucuronide conjugates representing 4.7–7.1% of AUC0–12 h and three less abundant metabolites (<0.2–1.9% AUC0–12 h). The most abundant metabolites in urine were two glucuronide conjugates (7.8–13.2% of dose) and in faeces was a tetrahydrofuran ring-opened carboxylic acid metabolite (1.9% of dose). 4. To conclude, empagliflozin was rapidly absorbed and excreted primarily unchanged in urine and faeces. Unchanged parent was the major drug-related component in plasma. Metabolism was primarily via glucuronide conjugation.