Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects

Ji Young Park, Kyoung Ah Kim, Jae Gook Shin, Ki Young Lee

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Aims: Fungal infection is a significant comorbidity in patients with diabetes mellitus, and ketoconazole, an antifungal agent, causes a number of drug interactions with coadministered drugs. Rosiglitazone is a novel thiazolidinedione antidiabetic drug, mainly metabolized by CYP2C8 and to a lesser extent CYP2C9. We investigated the possible effect of ketoconazole on the pharmacokinetics of rosiglitazone in humans. Methods: Ten healthy Korean male volunteers were treated twice daily for 5 days with 200 mg ketoconazole or with placebo, using a randomized, open-label, two-way crossover study. On day 5, a single dose of 8 mg rosiglitazone was administered orally, and plasma rosiglitazone concentrations were measured. Results: Ketoconazole increased the mean area under the plasma concentration-time curve for rosiglitazone by 47% [P = 0.0003; 95% confidence interval (CI) 23, 70] and the mean elimination half-life from 3.55 to 5.50 h (P = 0.0003; 95% CI in difference 1.1, 2.4). The peak plasma concentration of rosiglitazone was increased by ketoconazole treatment by 17% (P = 0.03; 95% CI 5, 29). The apparent oral clearance of rosiglitazone decreased by 28% after ketoconazole treatment (P = 0.0005; 95% CI 18, 38). Conclusions: This study revealed that ketoconazole affected the disposition of rosiglitazone in humans, probably by the inhibition of CYP2C8 and CYP2C9, leading to increasing rosiglitazone concentrations that could increase the efficacy of rosiglitazone or its adverse events.

Original languageEnglish
Pages (from-to)397-402
Number of pages6
JournalBritish Journal of Clinical Pharmacology
Issue number4
Publication statusPublished - 2004 Oct
Externally publishedYes


  • CYP2C8
  • Drug interaction
  • Ketoconazole
  • Pharmacokinetics
  • Rosiglitazone

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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