title: Pharmacokinetics and Pharmacodynamics of Henagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, in Chinese Patients with Type 2 Diabetes Mellitus.
abstract: OBJECTIVE
  Henagliflozin, a selective inhibitor of the renal sodium glucose cotransporter-2, was developed for type 2 diabetes mellitus (T2DM). This study characterized single- and multiple-dose pharmacokinetics and pharmacodynamics of henagliflozin in Chinese patients with T2DM.
  
  
  METHODS
  Thirty T2DM patients were randomized in a 4:1 ratio to orally receive either henagliflozin 5, 10, 20 mg/day or placebo for 10 days, except on day 2 and day 3. Pharmacokinetic and pharmacodynamic profiles were measured on day 1 and day 10.
  
  
  RESULTS
  Henagliflozin exhibited dose-proportional plasma concentrations with a half-life ranging from 9.1 to 14 h. Steady-state plasma henagliflozin concentration was reached by day 7 in all active treatment groups. Henagliflozin decreased the 24-h mean plasma glucose by -0.3, -1.0 and -1.0 mmol/L with doses of 5, 10 and 20 mg on day 1, respectively. The corresponding values on day 10 were -0.8, -0.9 and -1.2 mmol/L. Twenty-four-hour urinary glucose excretion increased by 11, 65 and 82 times with doses of 5, 10 and 20 mg on day 1, respectively, with a similar trend on day 10. No treatment-related serious adverse events or discontinuations due to adverse events occurred.
  
  
  CONCLUSIONS
  The observed pharmacokinetic and pharmacodynamic profiles of henagliflozin support a once-daily dosing regimen in Chinese T2DM patients.
authors.affiliation: Clinical Pharmacy Lab, General Hospital of Chengdu Military Region PLA, Chengdu, Sichuan, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yong
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
authors.affiliation: Department of Endocrine and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Clinical Medicine, Jiangsu Hengrui Medicine Co., Ltd., Shanghai, 200122, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Clinical Medicine, Jiangsu Hengrui Medicine Co., Ltd., Shanghai, 200122, China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Clinical Pharmacy Lab, General Hospital of Chengdu Military Region PLA, Chengdu, Sichuan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Clinical Pharmacy Lab, General Hospital of Chengdu Military Region PLA, Chengdu, Sichuan, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Clinical Medicine, Jiangsu Hengrui Medicine Co., Ltd., Shanghai, 200122, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Clinical Medicine, Jiangsu Hengrui Medicine Co., Ltd., Shanghai, 200122, China.
authors.forename: Minquan
authors.initials: M
authors.lastname: Wang
authors.affiliation: Clinical Pharmacy Lab, General Hospital of Chengdu Military Region PLA, Chengdu, Sichuan, China.
authors.forename: Lantian
authors.initials: L
authors.lastname: Wang
authors.affiliation: Clinical Pharmacy Lab, General Hospital of Chengdu Military Region PLA, Chengdu, Sichuan, China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Dai
authors.affiliation: Clinical Pharmacy Lab, General Hospital of Chengdu Military Region PLA, Chengdu, Sichuan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Clinical Medicine, Jiangsu Hengrui Medicine Co., Ltd., Shanghai, 200122, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Clinical Medicine, Jiangsu Hengrui Medicine Co., Ltd., Shanghai, 200122, China. maoweitaoliu@126.com.
authors.forename: Huaqiong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D044466:Asian People; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C000611095:henagliflozin; D005947:Glucose