Gemfibrozil considerably increases the plasma concentrations of rosiglitazone

Diabetologia. 2003 Oct;46(10):1319-23. doi: 10.1007/s00125-003-1181-x. Epub 2003 Jul 29.


Aims/hypothesis: Our aim was to investigate possible interaction between gemfibrozil and rosiglitazone, a thiazolidinedione antidiabetic drug.

Methods: In a randomised crossover study with two phases, 10 healthy volunteers took 600 mg gemfibrozil or placebo orally twice daily for 4 days. On day 3, they ingested a single 4 mg dose of rosiglitazone. Plasma rosiglitazone and its N-desmethyl metabolite concentrations were measured for up to 48 h.

Results: Gemfibrozil raised the mean area under the plasma rosiglitazone concentration-time curve (AUC) 2.3-fold (range 1.5- to 2.8-fold; p=0.00002) and prolonged the elimination half-life (t(1/2)) of rosiglitazone from 3.6 to 7.6 h ( p=0.000002). The peak plasma rosiglitazone concentration (C(max)) was increased only 1.2-fold (range 0.9- to 1.6-fold; p=0.01) by gemfibrozil, but gemfibrozil raised the plasma rosiglitazone concentration measured 24 h after dosing (C(24)) 9.8-fold (range, 4.5- to 33.6-fold; p=0.00008). In addition, gemfibrozil prolonged the t(max) of N-desmethylrosiglitazone from 7 to 12 h and reduced the N-desmethylrosiglitazone/rosiglitazone AUC(0-48) ratio by 38% ( p<0.01).

Conclusions/interpretation: Gemfibrozil raises the plasma concentrations of rosiglitazone probably by inhibiting the CYP2C8-mediated biotransformation of rosiglitazone. Co-administration of gemfibrozil, or another potent inhibitor of CYP2C8, and rosiglitazone could increase the efficacy but also the risk of concentration-dependent adverse effects of rosiglitazone.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Cross-Over Studies
  • Female
  • Gemfibrozil / blood
  • Gemfibrozil / pharmacology*
  • Half-Life
  • Humans
  • Hypoglycemic Agents / blood*
  • Hypolipidemic Agents / blood
  • Hypolipidemic Agents / pharmacology*
  • Male
  • Osmolar Concentration
  • Rosiglitazone
  • Thiazolidinediones / blood*
  • Time Factors


  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • N-desmethylrosiglitazone
  • Thiazolidinediones
  • Rosiglitazone
  • Gemfibrozil