European Journal of Clinical Pharmacology

, Volume 63, Issue 7, pp 677–686 | Cite as

The influence of hepatic impairment on the pharmacokinetics of the dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptin

  • Y.-L. He
  • R. Sabo
  • J. Campestrini
  • Y. Wang
  • M. Ligueros-Saylan
  • K. C. Lasseter
  • S. C. Dilzer
  • D. Howard
  • W. P. Dole
Pharmacokinetics and Disposition

Abstract

Objective

Vildagliptin is a potent and selective dipeptidyl peptidase-IV (DPP-4) inhibitor that improves glycemic control in patients with type 2 diabetes mellitus by increasing α- and β-cell responsiveness to glucose. This study investigated the pharmacokinetics of vildagliptin in patients with hepatic impairment compared with healthy subjects.

Methods

This was an open-label, parallel-group study in patients with mild (n = 6), moderate (n = 6) or severe (n = 4) hepatic impairment and healthy subjects (n = 6). All subjects received a single 100-mg oral dose of vildagliptin, and plasma concentrations of vildagliptin and its main pharmacologically inactive metabolite LAY151 were measured up to 36 h post-dose.

Results

Exposure to vildagliptin (AUC0–∞ and Cmax) decreased non-significantly by 20 and 30%, respectively, in patients with mild hepatic impairment [geometric mean ratio (90% CI): AUC0–∞, 0.80 (0.60, 1.06), p = 0.192; Cmax, 0.70 (0.46, 1.05), p = 0.149]. Exposure to vildagliptin was also decreased non-significantly in patients with moderate hepatic impairment [−8% for AUC0–∞, geometric mean ratio (90% CI): 0.92 (0.69, 1.23), p = 0.630; −23% for Cmax, geometric mean ratio (90% CI): 0.77 (0.51, 1.17), p = 0.293]. In patients with severe hepatic impairment, Cmax was 6% lower than that in healthy subjects [geometric mean ratio (90% CI): 0.94 (0.59, 1.49), p = 0.285], whereas AUC0–∞ was increased by 22% [geometric mean ratio (90% CI): 1.22 (0.89, 1.68), p = 0.816). Across the hepatic impairment groups, LAY151 AUC0–∞ and Cmax were increased by 29–84% and 24–63%, respectively, compared with healthy subjects. The single 100-mg oral dose of vildagliptin was well tolerated by patients with hepatic impairment.

Conclusions

There was no significant difference in exposure to vildagliptin in patients with mild, moderate or severe hepatic impairment; therefore, no dose adjustment of vildagliptin is necessary in patients with hepatic impairment.

Keywords

Chronic liver disease Dipeptidyl peptidase-IV inhibitor Pharmacokinetics Type 2 diabetes Vildagliptin 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Y.-L. He
    • 1
  • R. Sabo
    • 2
  • J. Campestrini
    • 3
  • Y. Wang
    • 2
  • M. Ligueros-Saylan
    • 2
  • K. C. Lasseter
    • 4
  • S. C. Dilzer
    • 4
  • D. Howard
    • 2
  • W. P. Dole
    • 1
  1. 1.Exploratory DevelopmentNovartis Institutes for Biomedical Research, Inc.CambridgeUSA
  2. 2.Novartis Pharmaceuticals CorporationEast HanoverUSA
  3. 3.Novartis Pharma SARueil-MalmaisonFrance
  4. 4.Pharmanet Development GroupMiamiUSA

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