Pharmacokinetics of repaglinide in subjects with renal impairment

Clin Pharmacol Ther. 2000 Jan;67(1):7-15. doi: 10.1067/mcp.2000.103973.


Objective: To evaluate the effect of renal impairment and renal failure on the pharmacokinetics and safety of repaglinide.

Methods: We conducted a phase I, multicenter, parallel-group, pharmacokinetic comparison trial with single and multiple doses of repaglinide in subjects with various degrees of renal impairment. Subjects with normal renal function (n = 6) and subjects with renal impairment (mild to moderate, n = 6; severe, n = 6) received treatment with 2 mg repaglinide for 7 days. Subjects in the hemodialysis group (n = 6) received two single doses of 2 mg repaglinide separated by a 7- to 14-day washout period. All subjects had repaglinide serum pharmacokinetic profiles measured for the first and last doses administered. Serum steady-state levels, urine levels, and dialysate levels were also measured.

Results: Pharmacokinetic parameters did not show significant changes after single or multiple doses of repaglinide, although the elimination rate constant in the group with severe renal impairment decreased after 1 week of treatment. Subjects with severe impairment had significantly higher area under the curve values after single and multiple doses of repaglinide than subjects with normal renal function. No significant differences in values for maximum serum concentration or time to reach maximum concentration were detected between subjects with renal impairment and those with normal renal function. Hemodialysis did not significantly affect repaglinide clearance.

Conclusions: Repaglinide was safe and well tolerated in subjects with varying degrees of renal impairment. Although adjustment of starting doses of repaglinide is not necessary for renal impairment or renal failure, severe impairment may require more care when upward adjustments of dosage are made.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Area Under Curve
  • Carbamates / administration & dosage
  • Carbamates / blood
  • Carbamates / pharmacokinetics*
  • Carbamates / urine
  • Creatinine / blood
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / urine
  • Kidney Diseases / blood*
  • Kidney Diseases / therapy
  • Male
  • Middle Aged
  • Piperidines / administration & dosage
  • Piperidines / blood
  • Piperidines / pharmacokinetics*
  • Piperidines / urine
  • Protein Binding
  • Renal Dialysis
  • Severity of Illness Index


  • Carbamates
  • Hypoglycemic Agents
  • Piperidines
  • repaglinide
  • Creatinine