Increased bioavailability of phenylephrine by co-administration of acetaminophen: results of four open-label, crossover pharmacokinetic trials in healthy volunteers.

Purpose: Over-the-counter combinations containing acetaminophen and phenylephrine for treatment of the common cold and influenza are widespread, but there are few data about pharmacokinetics of these two drugs used in combination. We aimed to investigate pharmacokinetic interactions between acetamin...

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Publicado en:European Journal of Clinical Pharmacology Vol. 71; no. 2; pp. 151 - 159
Autores principales: Atkinson, Hartley, Stanescu, Ioana, Salem, Isam, Potts, Amanda, Anderson, Brian
Formato: research tables/charts randomized controlled trial Journal Article
Publicado: Springer Nature Feb2015
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Feb2015
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      pub: Springer Nature
      place: New York, New York
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        atl: Increased bioavailability of phenylephrine by co-administration of acetaminophen: results of four open-label, crossover pharmacokinetic trials in healthy volunteers.
      aug:
        au:
          Atkinson, Hartley
          Stanescu, Ioana
          Salem, Isam
          Potts, Amanda
          Anderson, Brian
        affil: AFT Pharmaceuticals Ltd, Takapuna Auckland 0740 New Zealand
      sug:
        subj:
          Phenylephrine Administration and Dosage
          Phenylephrine Pharmacokinetics
          Biological Availability
          Acetaminophen Administration and Dosage
          Acetaminophen Pharmacokinetics
          Drug Interactions
          Human
          Randomized Controlled Trials
          Crossover Design
          Common Cold Drug Therapy
          Descriptive Statistics
          Confidence Intervals
          Jordan Ethnology
          Male
          Adolescence
          Adult
          Analysis of Variance
          Wilcoxon Signed Rank Test
          Funding Source
          Adolescent: 13-18 years
          Adult: 19-44 years
          Male
      ab: Purpose: Over-the-counter combinations containing acetaminophen and phenylephrine for treatment of the common cold and influenza are widespread, but there are few data about pharmacokinetics of these two drugs used in combination. We aimed to investigate pharmacokinetic interactions between acetaminophen and phenylephrine. Methods: A series of four randomised, open-label, crossover studies investigating phenylephrine and acetaminophen combination pharmacokinetics were undertaken ( n = 28, 30, 6 and 26) using standard non-compartmental analyses. Time-concentration observations from these four studies were pooled to examine the interaction between these two compounds. Data were analysed using non-linear mixed effects models. Results: Non-compartmental analyses showed an approximate doubling of phenylephrine plasma concentration when the standard 10-mg dose was administered in combination with acetaminophen. Population analysis was based on data from 90 subjects with 2050 observations. The relative bioavailability of phenylephrine 10 mg was doubled (Fbio 2.11, 95%CI 1.89, 2.31) when combined with acetaminophen 1000 mg, while the absorption half-time was reduced by 50 %. When combined with 500 mg of acetaminophen, bioavailability increased by 64 % (Fbio 1.64). Phenylephrine 5 mg in combination with acetaminophen 1000 mg produced a phenylephrine plasma time-concentration profile similar to that seen with phenylephrine 10 mg administered alone. Conclusions: The relative bioavailability of phenylephrine was increased when co-administered with acetaminophen.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        randomized controlled trial
        Journal Article
      ougenre: Article
    language: English
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