Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects.

Background: Efforts to lower plasma lipid levels sometimes require multiple agents with different mechanisms of action to achieve results specified by national treatment guidelines. Methods: This was an open-label, randomized, three-period, multiple-dose crossover study that assessed the potential f...

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Published in:European Journal of Clinical Pharmacology Vol. 67; no. 5; pp. 483 - 493
Main Authors: Kosoglou, Teddy, Zhu, Yali, Statkevich, Paul, Triantafyllou, Ilias, Taggart, William, Xuan, Fengjuan, Kim, Kenneth, Cutler, David
Format: clinical trial research tables/charts Journal Article
Published: Springer Nature May2011
Online Access:View this record in EBSCOhost
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      dt: May2011
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-010-0955-6
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        atl: Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects.
      aug:
        au:
          Kosoglou, Teddy
          Zhu, Yali
          Statkevich, Paul
          Triantafyllou, Ilias
          Taggart, William
          Xuan, Fengjuan
          Kim, Kenneth
          Cutler, David
        affil: Merck & Co., Inc., Whitehouse Station USA
      sug:
        subj:
          Drug Interactions
          Ezetimibe Simvastatin Pharmacokinetics
          Niacin Pharmacokinetics
          Niacin Administration and Dosage
          Ezetimibe Simvastatin Administration and Dosage
          Hyperlipidemia Drug Therapy
          Funding Source
          Human
          Clinical Trials
          Crossover Design
          Delayed-Action Preparations
          Descriptive Statistics
          Drug Therapy, Combination
          Male
          Female
          Biological Availability
          Confidence Intervals
          Analysis of Variance
          Adult
          Middle Age
          Ezetimibe Simvastatin Blood
          Niacin Blood
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Male
          Female
      ab: Background: Efforts to lower plasma lipid levels sometimes require multiple agents with different mechanisms of action to achieve results specified by national treatment guidelines. Methods: This was an open-label, randomized, three-period, multiple-dose crossover study that assessed the potential for pharmacokinetic interaction between extended-release niacin and ezetimibe/simvastatin and their major metabolites. Eighteen adults received three randomized treatments: (A) extended-release (ER) niacin 1000 mg/day for 2 days, followed by 2000 mg/day for 5 days; (B) ezetimibe/simvastatin 10 mg/20 mg/day; (C) coadministration of Treatments A and B. Treatments were given once a day after a low fat breakfast for a total of 7 days, with a 7-day inter-dose period. Results: There were small (mean ≤35%) increases in drug exposure for all analytes after coadministration of ER niacin and ezetimibe/simvastatin 10 mg/20 mg. The least-square mean between treatment C (maximum plasma concentration) ratios (×100) were 97, 98, and 109% for ezetimibe, simvastatin and niacin, respectively. The corresponding ratios for total ezetimibe, simvastatin acid, and nicotinuric acid were 99, 118, and 110%. The AUC (area under the plasma concentration-time curve from time zero to 24 h after dosing) ratios for ezetimibe, simvastatin, and niacin were 109, 120, and 122%, respectively, and the corresponding ratios for total ezetimibe, simvastatin acid, and nicotinuric acid were 126, 135 and 119%. Conclusion: There is a small pharmacokinetic drug interaction between ER niacin and ezetimibe/simvastatin and although this is not considered to be clinically significant, the concomitant use of these drugs should be appropriately monitored, especially during the niacin titration period.
      pubtype: Academic Journal
      doctype:
        clinical trial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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