Pharmacokinetics, pharmacodynamics, and safety of clevidipine after prolonged continuous infusion in subjects with mild to moderate essential hypertension.

Purpose: Clevidipine is a rapidly-acting intravenous dihydropyridine antihypertensive acting via calcium channel blockade. This was a randomized, single-blind, parallel-design study of a 72-h continuous clevidipine infusion. Method: Doses of 2, 4, 8, or 16.0 mg/h or placebo were evaluated in 61 subj...

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Publicado en:European Journal of Clinical Pharmacology Vol. 68; no. 10; pp. 1385 - 1395
Autores principales: Smith, William, Marbury, Thomas, Komjathy, Steven, Sumeray, Mark, Williams, Gregory, Hu, Ming-yi, Mould, Diane
Formato: research tables/charts randomized controlled trial Journal Article
Publicado: Springer Nature Oct2012
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Oct2012
      vid: 68
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      pub: Springer Nature
      place: New York, New York
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        atl: Pharmacokinetics, pharmacodynamics, and safety of clevidipine after prolonged continuous infusion in subjects with mild to moderate essential hypertension.
      aug:
        au:
          Smith, William
          Marbury, Thomas
          Komjathy, Steven
          Sumeray, Mark
          Williams, Gregory
          Hu, Ming-yi
          Mould, Diane
        affil: Volunteer Research Group, University of Tennessee Medical Center, Knoxville USA
      sug:
        subj:
          Clevidipine Butyrate Pharmacokinetics
          Clevidipine Butyrate Pharmacodynamics
          Clevidipine Butyrate Administration and Dosage
          Infusions, Intravenous
          Hypertension Drug Therapy
          Antihypertensive Agents Therapeutic Use
          Randomized Controlled Trials
          Clevidipine Butyrate Blood
          Safety
          Single-Blind Studies
          Human
          Random Assignment
          Male
          Female
          Placebos
          Dose-Response Relationship, Drug
          Regression
          Descriptive Statistics
          Chromatography, Liquid Methods
          Mass Spectrometry Methods
          Data Analysis Software
          Post Hoc Analysis
          Electrocardiography Methods
          Middle Age
          Clevidipine Butyrate Adverse Effects
          Clevidipine Butyrate Metabolism
          Funding Source
          Middle Aged: 45-64 years
          Male
          Female
      ab: Purpose: Clevidipine is a rapidly-acting intravenous dihydropyridine antihypertensive acting via calcium channel blockade. This was a randomized, single-blind, parallel-design study of a 72-h continuous clevidipine infusion. Method: Doses of 2, 4, 8, or 16.0 mg/h or placebo were evaluated in 61 subjects with mild to moderate essential hypertension. IV clevidipine or placebo was initiated at 2.0 mg/h and force-titrated in doubling increments every 3 min to target dose, then maintained for 72 h. Blood pressure and heart rate were measured during infusion, and for 4, 6 and 8 h after termination of infusion, although oral therapy could be restarted at 4 h. Clevidipine blood levels were obtained during infusion and for 1 hour after termination. Results: Rapid onset of drug effect occurred at all clevidipine dose levels, with consistent pharmacokinetics and rapid offset after 72-h infusion. No evidence of tolerance to the clevidipine drug effect was observed at any dose level over the 72-h infusion. No evidence of rebound hypertension was found for either 4 or 6 h after termination of the clevidipine infusion. At 8 h following cessation of clevidipine, blood pressure was not significantly higher than at baseline. Placebo-treated subjects had blood pressures lower than baseline at 8 h following infusion termination; hence, placebo-adjusted blood pressures tended to be slightly higher than baseline. Conclusion: This study supports the use of up to 72 h of IV clevidipine therapy for the management of blood pressure, with consistent pharmacokinetic/pharmacodynamic characteristics and context insensitive half-life across the dose ranges evaluated.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        randomized controlled trial
        Journal Article
      ougenre: Article
    language: English
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