Effect of Cilostazol on the Pharmacokinetics of Simvastatin in Healthy Subjects.

Purpose. We evaluated potential drug-drug interactions between cilostazol and simvastatin, both CYP3A substrates, in healthy subjects. Methods. An open-label, two-period, fixed-sequence clinical study was conducted. Seventeen subjects were given a single oral dose of simvastatin 40 mg on day 1 and m...

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Publicado en:BioMed Research International pp. 1 - 7
Autores principales: Kim, Jung-Ryul, Jung, Jin Ah, Kim, Seokuee, Huh, Wooseong, Ghim, Jong-Lyul, Shin, Jae-Gook, Ko, Jae-Wook
Formato: clinical trial research tables/charts Journal Article
Publicado: Wiley-Blackwell 1/9/2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 1/9/2019
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        134045239
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        134045239
        10.1155/2019/1365180
        134045239
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        atl: Effect of Cilostazol on the Pharmacokinetics of Simvastatin in Healthy Subjects.
      aug:
        au:
          Kim, Jung-Ryul
          Jung, Jin Ah
          Kim, Seokuee
          Huh, Wooseong
          Ghim, Jong-Lyul
          Shin, Jae-Gook
          Ko, Jae-Wook
        affil: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea
      sug:
        subj:
          Cilostazol Pharmacodynamics
          Simvastatin Pharmacokinetics
          Drug Interactions
          Cytochrome P-450 Enzyme System Drug Effects
          Cytochrome P-450 Enzyme System Metabolism
          Human
          Clinical Trials
          Simvastatin Blood
          Chromatography, Liquid
          Mass Spectrometry
          Descriptive Statistics
          Confidence Intervals
          Cholesterol Blood
          Triglycerides Blood
      ab: Purpose. We evaluated potential drug-drug interactions between cilostazol and simvastatin, both CYP3A substrates, in healthy subjects. Methods. An open-label, two-period, fixed-sequence clinical study was conducted. Seventeen subjects were given a single oral dose of simvastatin 40 mg on day 1 and multiple oral doses of cilostazol 100 mg twice daily on days 2 to 5 followed by a single dose of cilostazol and simvastatin on day 6. Plasma concentrations of simvastatin and its active metabolite, simvastatin acid, were measured using liquid chromatography-tandem mass spectrometry for pharmacokinetic assessment. Moreover, serum lipid profiles under fasting conditions were determined. Results. The geometric mean ratios of the area under the plasma concentration-time curve from time zero to time infinity of simvastatin combined with cilostazol to that of simvastatin alone were 1.64 (90% CI, 1.38-1.95) for simvastatin and 1.31 (1.04-1.66) for simvastatin acid. In addition, coadministration with cilostazol significantly increased the maximum concentration of simvastatin and simvastatin acid, up to 1.8-fold and 1.6-fold, respectively. However, the effects of a single dose of simvastatin on serum lipid profiles were not affected notably when simvastatin was coadministered with cilostazol. Conclusions. Multiple doses of cilostazol increased the systemic exposure of simvastatin and simvastatin acid following a single dose of simvastatin.
      pubtype: Academic Journal
      doctype:
        clinical trial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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