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Pharmacokinetic Profile of Dextromethorphan Hydrobromide in a Syrup Formulation in Children and Adolescents

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Abstract

Background

Dextromethorphan hydrobromide (DM) is a widely used antitussive. This study determined, for the first time, the basic pharmacokinetic profile of DM and its active metabolite, dextrorphan (DP) in children and adolescents.

Methods

Thirty-eight male and female subjects at risk for developing an upper respiratory tract infection (URTI), or symptomatic with cough due to URTI, were enrolled in this single-dose, open-label study: ages 2–5 years (Group A, n = 8), 6–11 years (Group B, n = 17), 12–17 years (Group C, n = 13). Subjects were genotyped for cytochrome P450 (CYP) 2D6 polymorphisms and characterized as poor (PM) or non-poor metabolizers (non-PM). Groups A and B were dosed using an age–weight dosing schedule (DM range 7.5–24.75 mg); a 30-mg dose was used for Group C.

Results

Average exposures to total DP increased as age group increased, and average exposure to DM was highest in the adolescent group. One subject in that group was a PM. The terminal half-life (t ½) values were longer in the adolescent group due in part to the single PM subject. No relationship between body weight and pharmacokinetic parameters was noted.

Conclusions

This is the first evaluation of the pharmacokinetic characteristics of DM in children and adolescents. A single dose of DM in this population was safe, and well tolerated at all doses tested. The data are used to model and compare pediatric DM exposures with those of adults.

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Acknowledgments

We thank Advanced Biomedical Research, Inc. who performed the data management, statistical and pharmacokinetic analysis, and report writing for this study. We thank Vincent Fabien who was the study statistician employed at Novartis Consumer Health, S.A. We also appreciate the assistance with manuscript preparation provided by Mark Calcamuggio (The Write Company, LLC) and further technical review and editorial assistance by Dr. Judith Rosen Farrar (Life Sciences Press, LLC).

Financial Disclosure

This study was sponsored by Novartis Consumer Health, Inc., which also provided support for manuscript preparation. The latter consisted solely of editing and formatting for journal submission with no contribution to content.

The material in this manuscript represents original material and has not been submitted or published elsewhere. Eric Guenin was an employee of Novartis Consumer Health, Inc. at the time of the study and writing of the manuscript; he is now employed at Reckitt Benckiser. Marianna Armogida is an employee of Novartis Consumer Health, S.A. Dennis Riff was the principal investigator and is an employee of Advanced Clinical Research Institute.

Authorship Statement

All authors were fully involved in developing and conducting the study, evaluating the data and writing/editing this manuscript. The paper meets the authorship requirements of the International Committee of Medical Journal Editors.

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Correspondence to Eric Guenin.

Additional information

At the time the study was conducted, Dr. Guenin held the position of Director, Clinical Research, Novartis Consumer Health, Inc., Parsippany, NJ, USA.

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Guenin, E., Armogida, M. & Riff, D. Pharmacokinetic Profile of Dextromethorphan Hydrobromide in a Syrup Formulation in Children and Adolescents. Clin Drug Investig 34, 609–616 (2014). https://doi.org/10.1007/s40261-014-0210-5

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