title: Biotransformation and mass balance of the SGLT2 inhibitor empagliflozin in healthy volunteers.
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 [(14)C]-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.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, CT , USA .
authors.forename: Lin-Zhi
authors.initials: LZ
authors.lastname: Chen
authors.forename: Arvid
authors.initials: A
authors.lastname: Jungnik
authors.forename: Yanping
authors.initials: Y
authors.lastname: Mao
authors.forename: Elsy
authors.initials: E
authors.lastname: Philip
authors.forename: Dale
authors.initials: D
authors.lastname: Sharp
authors.forename: Anna
authors.initials: A
authors.lastname: Unseld
authors.forename: Leo
authors.initials: L
authors.lastname: Seman
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Woerle
authors.forename: Sreeraj
authors.initials: S
authors.lastname: Macha
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005960:Glucosides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin
keywords: Absorption; excretion; metabolic pathway; metabolite; pharmacokinetics; radiolabeled