title: Pharmacokinetic and Pharmacodynamic Properties and Tolerability of Single- and multiple-dose Once-daily Empagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, in Chinese Patients With Type 2 Diabetes Mellitus.
abstract: OBJECTIVE
  The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties and tolerability of the oral once-daily sodium glucose cotransporter 2 inhibitor empagliflozin, given in single and multiple 10 and 25 mg doses in Chinese patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  In a double-blind, placebo-controlled, parallel-group study, Chinese patients with T2DM were randomly assigned to receive a single dose of empagliflozin 10 or 25 mg or placebo on day 1 and once daily on days 3 to 9.
  
  
  RESULTS
  A total of 24 patients were enrolled (14 men, 10 women; median age, 53.5 years; empagliflozin 10 mg, n = 9; empagliflozin 25 mg, n = 9; and placebo, n = 6). After both single- and multiple-dose administration, empagliflozin 10 and 25 mg were rapidly absorbed, reaching peak plasma concentrations within 1 to 1.5 hours (median), with plasma levels declining biphasically. Empagliflozin exposure increased roughly dose proportionally between 10 and 25 mg. Mean terminal elimination half-life values at steady state were 13.9 and 12.1 hours with empagliflozin 10 and 25 mg, respectively. Mean (SD) changes from baseline in 24-hour urinary glucose excretion (UGE) on day 1 were +87.7 (22.9) and +82.8 (18.8) g with empagliflozin 10 and 25 mg, respectively, compared with -1.0 (2.8) g with placebo, and on day 9 were +95.8 (24.1), +82.6 (34.8) g with empagliflozin 10 and 25 mg, respectively, compared with -4.1 (6.4) g with placebo. Mean (SD) changes from baseline in fasting plasma glucose (FPG) on day 2 were -18.7 (17.2) mg/dL and -25.8 (19.6) mg/dL with empagliflozin 10 and 25 mg, respectively, compared with -4.2 (15.2) mg/dL with placebo, and on day 9, were -25.6 (20.7) mg/dL and -31.4 (26.9) mg/dL with empagliflozin 10 and 25 mg, respectively, compared to -3.7 (7.5) mg/dL with placebo. On day 10, mean changes in weight were -1.1, -1.6, and +0.5 kg with empagliflozin 10 and 25 mg and placebo, respectively. Overall, empagliflozin 10 and 25 mg had safety profiles similar to that of placebo. There were no reports of hypoglycemia, urinary tract infections, or genital infections.
  
  
  CONCLUSIONS
  Results with single and multiple doses of empagliflozin 10 and 25 mg suggest linear pharmacokinetic properties in Chinese patients with T2DM, with a safety profile similar to that of placebo. Empagliflozin treatment was associated with increases in UGE and reductions in FPG compared with placebo. ClinicalTrials.gov identifier: NCT01316341.
authors.affiliation: Peking University First Hospital, Beijing, People׳s Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Peking University First Hospital, Beijing, People׳s Republic of China. Electronic address: cuiymzy@126.com.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Boehringer Ingelheim Corporation, Shanghai, People׳s Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lang
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut, USA.
authors.forename: Afshin
authors.initials: A
authors.lastname: Salsali
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pinnetti
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut, USA.
authors.forename: Sreeraj
authors.initials: S
authors.lastname: Macha
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D006029:Glycosuria / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin
keywords: Chinese patients; empagliflozin; fasting plasma glucose; pharmacokinetics; urinary glucose excretion