Biotransformation and mass balance of the SGLT2 inhibitor empagliflozin in healthy volunteers. (June 2015)

• Record Type: Journal Article
• Authors: Chen, Lin-Zhi; Jungnik, Arvid; Mao, Yanping; Philip, Elsy; Sharp, Dale; Unseld, Anna; Seman, Leo; Woerle, Hans-Jürgen; Macha, Sreeraj
• Is Part Of: Xenobiotica. Volume 45:Number 6(2015:Jun.)
• Page Start: 520
• Page End: 529
• Publication Date: 2015-06
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2014.999141
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title>Abstract</title> <p>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 [<sup>14</sup>C]-empagliflozin.</p> <p>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%.</p> <p>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 AUC<sub>0–12 h</sub>. 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 AUC<sub>0–12 h</sub> and three less abundant metabolites (<0.2–1.9% AUC<sub>0–12 h</sub>). 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).</p> <p>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.</p> </abstract>