Effect of naproxen on the hypothalamic–pituitary– adrenal axis in healthy volunteers

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In patients with rheumatoid arthritis (RA) the activity of the hypothalamic– pituitary–adrenal (HPA) axis is decreased. WHAT THIS STUDY ADDS • It is not known how the frequent use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in patients with RA influenc...

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Published in:	British journal of clinical pharmacology Vol. 67; no. 1; pp. 22 - 28
Main Authors:	Eijsbouts, Agnes M. M., Kempers, Marlies J. E., Kramer, Renske S. A., Hopman, Maria T. E., Van Den Hoogen, Frank H. J., Laan, Ronald F. J. M., Hermus, Ad R. M. M., Sweep, Fred C. G. J., Van De Putte, Leo B. A.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-01-2009 Blackwell Blackwell Science Inc
Subjects:	Adolescent Adrenocorticotropic Hormone - blood Adult Anti-Inflammatory Agents, Non-Steroidal - pharmacology Biological and medical sciences Circadian Rhythm Double-Blind Method Exercise Test Female Humans Hydrocortisone - metabolism Hypothalamic–pituitary–adrenal axis Hypothalamo-Hypophyseal System - drug effects Male Medical sciences Middle Aged naproxen Naproxen - pharmacology NSAID Pharmacodynamics Pharmacology. Drug treatments Pituitary-Adrenal System - drug effects Saliva - chemistry Young Adult Human Prostaglandin-endoperoxide synthase Healthy subject Hypothalamohypophysoadrenal axis Enzyme NSAID Enzyme inhibitor Hypothalamic-pituitary-adrenal axis Non steroidal antiinflammatory agent Analgesic Naproxen Antipyretic Arylpropionic acid derivatives Oxidoreductases
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Summary:	WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In patients with rheumatoid arthritis (RA) the activity of the hypothalamic– pituitary–adrenal (HPA) axis is decreased. WHAT THIS STUDY ADDS • It is not known how the frequent use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in patients with RA influences the HPA axis. • In this study the effect of the NSAID naproxen on HPA axis activity was tested in healthy volunteers. • Two weeks' use of naproxen did not influence the activity of the HPA axis in healthy volunteers under basal circumstances, nor in response to physical stress. AIM To study the effect of the nonsteroidal anti‐inflammatory drug naproxen on the activity of the hypothalamic–pituitary–adrenal (HPA) axis in healthy volunteers. METHODS A double‐blind, randomized study in two groups of 20 healthy volunteers was performed. The activity of the HPA axis was measured before and after the use of naproxen or placebo during a period of 2 weeks. Basal plasma adrenocorticotropic hormone (ACTH) and cortisol, 24‐h urinary cortisol, and circadian cortisol rhythm in saliva were determined. Plasma ACTH and cortisol were also measured during submaximal physical exercise. RESULTS There were no significant differences between the placebo and naproxen groups in basal plasma ACTH [09.00 h 3.1 pmol l−1, 95% confidence interval (CI) 2.0, 4.2, and 2.8 pmol l−1, 95% CI 1.9, 3.7, respectively], cortisol levels (09.00 h 0.45 µmol l−1, 95% CI 0.39, 0.51, and 0.40 µmol l−1, 95% CI 0.35, 0.44, respectively), 24 h urinary cortisol excretion (67.5 nmol 24 h−1, 95% CI 54.3, 80.7, and 86.8 nmol 24 h−1, 95% CI 54.4, 119.2, respectively), circadian cortisol rhythm measured in salivary samples, or ACTH and cortisol concentrations after physical exercise. After the use of placebo or naproxen for 2 weeks, no significant change in any of the parameters occurred (ACTH 09.00 h 3.0 pmol l−1, 95% CI 2.0, 3.9, and 3.0 pmol l−1, 95% CI 2.2, 3.8, respectively; cortisol 09.00 h 0.45 µmol l−1, 95% CI 0.37, 0.52, and 0.39 µmol l−1, 95% CI 0.34, 0.44, respectively; cortisol urine 79.5 nmol 24 h−1, 95% CI 59.5, 99.4, and 81.7 nmol 24 h−1, 95% CI 64.0, 99.4, respectively), and no significant differences were found in these parameters between the placebo and naproxen groups. CONCLUSIONS The use of naproxen does not influence the activity of the HPA axis in healthy volunteers under basal circumstances or in response to physical stress.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-News-1 ObjectType-Feature-3 content type line 23
ISSN:	0306-5251 1365-2125
DOI:	10.1111/j.1365-2125.2008.03324.x