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

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An Erratum to this article was published on 14 April 2015

Abstract

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.

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Acknowledgments

We thank the staff at IPRC for the administration of the study protocol and data collection. We are grateful to the volunteers who participated in this study. These studies were funded by AFT Pharmaceuticals Ltd, Auckland, New Zealand.

Conflict of interests

H Atkinson is a shareholder and Managing Director, and I Stanescu is an employee of AFT Pharmaceuticals Ltd. I Salem is an employee of IPRC. A Potts provides consultancy services to AFT Pharmaceuticals Ltd.

Author contributions

H Atkinson supervised the projects and was involved in the design of the study, development of the protocol, interpretation of the data and writing of the manuscript. I Stanescu contributed to the study design, protocol development, data analysis, interpretation and writing of the manuscript. I Salem contributed to study design, oversaw the administration of the study protocols and development of the drug assay, contributed to data interpretation and reviewed the manuscript. A Potts contributed to study design, protocol development, interpretation and writing of the manuscript. B Anderson was involved in data interpretation and critically reviewed the manuscript. All authors had full access to all the data.

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Authors and Affiliations

  1. AFT Pharmaceuticals Ltd, P O Box 33–203, Takapuna, Auckland, 0740, New Zealand

    Hartley C. Atkinson & Ioana Stanescu

  2. International Pharmaceutical Research Centre, 1 Queen Rania Street - Sport City Circle, Amman, 11196, Jordan

    Isam I. Salem

  3. Clinical Solutions NZ Ltd, Oaia Road, Waimauku, 0881, New Zealand

    Amanda L. Potts

  4. Department of Anaesthesiology, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Brian J. Anderson

Authors
  1. Hartley C. Atkinson
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  2. Ioana Stanescu
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  3. Isam I. Salem
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  4. Amanda L. Potts
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  5. Brian J. Anderson
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Corresponding author

Correspondence to Brian J. Anderson.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Figure S1

Flow of Participant Screening, Enrolment, and Participation for all four studies (GIF 192 kb)

High resolution image (EPS 10111 kb)

Figure S2

Visual predictive check for the phenylephrine PK model. All plots show median and 90% intervals (solid and dashed lines). Left hand plot shows all prediction corrected observed concentrations. Right hand plot shows prediction corrected percentiles (10%, 50%, and 90%) for observations (lines with symbols) and predictions (lines) with 95% confidence intervals for prediction percentiles (gray shaded areas). (GIF 229 kb)

High resolution image (EPS 2640 kb)

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(DOCX 41 kb)

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Atkinson, H.C., Stanescu, I., Salem, I.I. et al. Increased bioavailability of phenylephrine by co-administration of acetaminophen: results of four open-label, crossover pharmacokinetic trials in healthy volunteers. Eur J Clin Pharmacol 71, 151–158 (2015). https://doi.org/10.1007/s00228-014-1788-5

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  • DOI: https://doi.org/10.1007/s00228-014-1788-5

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