These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The effects of febuxostat on the pharmacokinetic parameters of rosiglitazone, a CYP2C8 substrate.
    Author: Naik H, Wu JT, Palmer R, McLean L.
    Journal: Br J Clin Pharmacol; 2012 Aug; 74(2):327-35. PubMed ID: 22242967.
    Abstract:
    AIMS: To determine the effect of febuxostat on cytochrome P450 2C8 (CYP2C8) activity using rosiglitazone as a CYP2C8 substrate. METHODS: Healthy subjects received febuxostat 120 mg daily (regimen A) or matching placebo (regimen B) for 9 days along with a single oral dose of rosiglitazone 4 mg on day 5 in a double-blind, randomized, cross-over fashion (≥7 day washout between periods). Plasma samples for analysis of the impact of febuxostat on the pharmacokinetics (PK) of rosiglitazone and its metabolite, N-desmethylrosiglitazone, were collected for 120 h after co-administration. RESULTS: Of the 39 subjects enrolled, 36 completed the study and were included in the PK analyses. Rosiglitazone PK parameters were comparable between regimens A and B. Median time to maximal plasma concentration, mean maximal plasma concentration (C(max)), area under the concentration-time curve (AUC) from time zero to the last quantifiable concentration (AUC(0-tlqc)), AUC from time zero to infinity (AUC(0-∞)), and terminal elimination half-life for regimen A were 0.50 h, 308.6 ng ml⁻¹, 1594.9 ng h ml⁻¹, 1616.0 ng h ml⁻¹ and 4.1 h, respectively, and for regimen B they were 0.50 h, 327.6 ng ml⁻¹, 1564.5 ng h ml⁻¹, 1584.2 ng h ml⁻¹ and 4.0 h, respectively. Point estimates for the ratio of regimen A to regimen B (90% confidence intervals) for rosiglitazone C(max) , AUC(0-tlqc) and AUC(0-∞) central values were 0.94 (0.89-1.00), 1.02 (1.00-1.04) and 1.02 (1.00-1.04), respectively. CONCLUSIONS: Co-administration of febuxostat had no effect on rosiglitazone or N-desmethylrosiglitazone PK parameters, suggesting that febuxostat can be given safely with drugs metabolized through CYP2C8.
    [Abstract] [Full Text] [Related] [New Search]