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Eur J Intern Med. 2013 Dec;24(8):698-706. doi: 10.1016/j.ejim.2013.03.019. Epub 2013 Apr 21.

Circadian rhythms and medical diseases: does it matter when drugs are taken?

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Clinica Medica, Azienda Ospedaliera-Universitaria, Ferrara, Italy. Electronic address:



Chronobiology is devoted to the study of biological rhythms. It is possible that a given medication may be therapeutic and safe when administered at some time, but subtherapeutic or poorly tolerated at another.


We focused on some classes of drugs, widely used by the internists, performing a PubMed search with the single drugs associated with the MeSH terms "Chronotherapy", "Circadian rhythm", and "Chronobiology, phenomena". Among the studies found, we considered only those provided with discrete numerosity or clearly stated methodological characteristics.


The results of available studies were given, along with a series of short take-home messages at the end of each mini-chapter devoted to: antihypertensives, statins, anticoagulants, analgesics, drugs for acid-related disorders, and anti-asthmatic drugs. In particular, evidence of morning vs. evening administration, when applicable, was given for each medication.


Adequate evidence seems to support that at least ACE-inhibitors or angiotensin receptor blockers, simvastatin, corticosteroids (slow-release formulation) for arthritic patients, and ranitidine should preferably be administered in the evening. Morning dosing could be better for proton pump inhibitors, whereas time of administration is not crucial for asthma inhalation drugs. Studies are available for other drugs, but not so strong enough to draw definite conclusions. For now, we need prospective intervention trials specifically designed to investigate the long-term effects of a temporal approach to medical therapy. However, since switching to morning-evening administration or vice versa is simple and inexpensive, in some cases it could be considered, remembering that, in any case, adherence remains the crucial point.


Chronobiology; Chronotherapy; Circadian rhythm; Disease; Internal medicine

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