Pharmacokinetic, Pharmacodynamic, and Safety Profiles of Proline Henagliflozin in Chinese Subjects with Varying Degrees of Liver Dysfunction.

Proline henagliflozin, a novel selective inhibitor of sodium glucose cotransporter 2, is a treatment for type 2 diabetes mellitus. We designed a parallel‐group, open‐label, and multicenter study to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles of henagliflozin in Chine...

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Publicado en:Journal of Clinical Pharmacology Vol. 64; no. 8; pp. 1015 - 1023
Autores principales: Ding, Likun, Yang, Lin, Ren, Danjun, Gao, Xiaohua, Zhang, Juanli, Liu, Meiyou, Sun, Li, Diao, Qingbo, Feng, Sheng, Wen, Aidong, Wang, Jingwen
Formato: clinical trial pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell Aug2024
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Aug2024
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1002/jcph.2437
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        atl: Pharmacokinetic, Pharmacodynamic, and Safety Profiles of Proline Henagliflozin in Chinese Subjects with Varying Degrees of Liver Dysfunction.
      aug:
        au:
          Ding, Likun
          Yang, Lin
          Ren, Danjun
          Gao, Xiaohua
          Zhang, Juanli
          Liu, Meiyou
          Sun, Li
          Diao, Qingbo
          Feng, Sheng
          Wen, Aidong
          Wang, Jingwen
        affil: Department of Pharmacy, Xijing Hospital, the Fourth Military Medical University, Xi'an, China
      sug:
        subj:
          Sodium-Glucose Co-Transporter 2 Inhibitors Pharmacokinetics
          Sodium-Glucose Co-Transporter 2 Inhibitors Pharmacodynamics
          Sodium-Glucose Co-Transporter 2 Inhibitors Therapeutic Use
          Chinese Persons
          Liver Physiopathology
          Liver Diseases Drug Therapy
          Patient Safety
          Human
          Male
          Female
          Child
          Adult
          Middle Age
          Clinical Trials
          Multicenter Studies
          Hypoglycemic Agents
          Descriptive Statistics
          Creatinine
          Drug Efficacy
          Diabetes Mellitus, Type 2 Drug Therapy
          Child: 6-12 years
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Male
          Female
      ab: Proline henagliflozin, a novel selective inhibitor of sodium glucose cotransporter 2, is a treatment for type 2 diabetes mellitus. We designed a parallel‐group, open‐label, and multicenter study to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles of henagliflozin in Chinese subjects with varying degrees of liver dysfunction. Thirty‐two subjects were enrolled and divided into four groups based on liver function (normal liver function, mild, moderate, or severe liver dysfunction). The area under the plasma concentration from time zero to infinity of henagliflozin in subjects with mild liver dysfunction, moderate liver dysfunction, and severe liver dysfunction compared with normal liver function was increased by 137%, 197%, and 204%, respectively. The maximum plasma concentration was also increased by 123%, 129%, and 139%, respectively. PK parameters of three metabolites varied to different degrees in the liver dysfunction groups than in the normal liver function group. The mean accumulative excretion amounts and fraction of dose excreted in urine expressed as a percentage were all increased with the decrease of liver function. The PD parameters were significantly higher in liver dysfunction groups than those in the normal liver function group. However, the urine creatinine (UCr) was not significantly different among the groups. No notable adverse events or adverse drug reactions were observed. Due to the higher exposures in subjects with liver dysfunction, the benefit: risk ratio should be individually assessed because the long‐term safety profile and efficacy have not been specifically studied in this population.
      pubtype: Academic Journal
      doctype:
        clinical trial
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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