Advertisement

International Journal of Clinical Pharmacy

, Volume 35, Issue 3, pp 344–358 | Cite as

Timing is important in medication administration: a timely review of chronotherapy research

  • Gagandeep KaurEmail author
  • Craig Phillips
  • Keith Wong
  • Bandana Saini
Review Article

Abstract

Background Chronotherapy involves altering the timing of medication administration to improve the overall control of a disease and to minimise treatment side-effects, and is an emerging concept in the field of therapeutics. Aim The aim of this review is to conduct an in-depth analysis of the recent literature in order to identify and evaluate the evidence base for drug chronotherapy. Method A literature search was conducted in three databases (Medline, Embase, International Pharmaceutical Abstracts) using the search terms “Chronotherapy”, “Chronopharmacology”, “Chronopharmacokinetics”, “Chronopharmacodynamics”, “Chronoefficacy”, “Chronoformulation”, “Morning and Evening”, “Morning and Bedtime” and their combinations. The selection criteria for the inclusion of articles in the review included currency (years 2008–Aug 2011), publication in English language, studies done in Humans and non-review articles that pertained to ‘drug’ therapy. Results Our search revealed a total of 192 journal articles, of which 41 articles were selected for review. The specific hypothesis for the effectiveness of chronotherapy that was tested in these 41 studies was chronoeffectiveness (n = 34), followed by chronopharmacokinetics (n = 5), chronomodulation (n = 3) and chronopharmacodynamics (n = 2). The findings from two-thirds (n = 27) of the reviewed studies, support the notion of chronotherapy. Conclusion The review presents the scope of chronotherapy in drug utilization. We believe that the knowledge of chronotherapy is growing and the current research for chronotherapy is promisingly in the conceptualization or early experimental phase. Going forward, chronotherapy studies should also explore genetic, gender and age related differences. Preliminary screening of new drugs for chronotherapeutic potential may be a way of enhancing quality use of medicines.

Keywords

Chronoeffectiveness Chronomodulation Chronopharmacodynamics Chronopharmacokinetics Chronotherapy Drug therapy 

Notes

Acknowledgments

We would like to acknowledge the Faculty of Pharmacy, University of Sydney and the Woolcock Institute of Medical Research for providing infrastructure support.

Funding

None.

Conflicts of interest

Authors have no conflicts of interest to declare.

References

  1. 1.
    Lemmer B, Labrecque G. Chronopharmacology and chronotherapeutics: definitions and concepts. Chronobiol Int. 1987;4(3):319–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Smolensky MH. Chronobiology and chronotherapeutics. Applications to cardiovascular medicine. Am J Hypertens. 1996;9(4 Pt 3):11S–21S.PubMedGoogle Scholar
  3. 3.
    Lemmer B. Relevance for chronopharmacology in practical medicine. Semin Perinatol. 2000;24(4):280–90.PubMedCrossRefGoogle Scholar
  4. 4.
    Touitou Y, Haus E. Biologic rhythms in clinical and laboratory medicine. Special ed. Berlin: Springer; 1994.Google Scholar
  5. 5.
    Lemmer B. The clinical relevance of chronopharmacology in therapeutics. Pharmacol Res. 1996;33(2):107–15.PubMedCrossRefGoogle Scholar
  6. 6.
    Sobrino J, Casanas L, Izquierdo C, Clavell J. Circadian rhythm variability in arterial blood pressure. Rev Enferm. 2006;29(6):50–2.PubMedGoogle Scholar
  7. 7.
    Smolensky MH, Lemmer B, Reinberg AE. Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma. Adv Drug Deliv Rev. 2007;59(9–10):852–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Harkness JA, Richter MB, Panayi GS, Pette KVD, Unger A, Pownall R, et al. Circadian variation in disease activity in rheumatoid arthritis. BMJ. 1982;284(6315):551–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Bellamy N, Sothern RB, Campbell J, Buchanan WW. Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis. Ann Rheum Dis. 2002;61(12):1075–80.PubMedCrossRefGoogle Scholar
  10. 10.
    Quyyumi AA. Circadian rhythms in cardiovascular disease. Am Heart J. 1990;120(3):726–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Smolensky MH, Reinberg A, Labrecque G. Twenty-four hour pattern in symptom intensity of viral and allergic rhinitis: treatment implications. J Allergy Clin Immunol. 1995;95(5 Pt 2):1084–96.PubMedCrossRefGoogle Scholar
  12. 12.
    Mormont MC, Lévi F. Circadian-system alterations during cancer processes: a review. Int J Cancer. 1997;70(2):241–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Hart FD, Taylor RT, Huskisson EC. Pain at night. Lancet. 1970;1(7652):881–4.PubMedCrossRefGoogle Scholar
  14. 14.
    Björn L. Circadian rhythms and drug delivery. J Control Release. 1991;16(1–2):63–74.Google Scholar
  15. 15.
    Reinberg A, Smolensky MH. Circadian changes of drug disposition in man. Clin Pharmacokinet. 1982;7(5):401–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Scott Md AJ, LaDou J. Biological rhythms, shiftwork, and occupational health. In: Bingham E, Cohrssen B, Powell CH, editors. Patty’s toxicology. New York: Wiley; 2001.Google Scholar
  17. 17.
    Reinberg A. Recent advances in chronobiology. Acta Med Auxol. 1976;8(2):135–146.Google Scholar
  18. 18.
    Smolensky MH, D’Alonzo GE. Biologic rhythms and medicine. Am J Med. 1988;85(1B):34–46.PubMedCrossRefGoogle Scholar
  19. 19.
    Reinberg AE. Concepts in chronopharmacology. Annu Rev Pharmacol Toxicol. 1992;32:51–66.PubMedCrossRefGoogle Scholar
  20. 20.
    Reinberg A. New aspects of human chronopharmacology. Arch Toxicol. 1976;36(3–4):327–39.PubMedCrossRefGoogle Scholar
  21. 21.
    Ohdo S. Changes in toxicity and effectiveness with timing of drug administration: implications for drug safety. Drug Saf. 2003;26(14):999–1010.PubMedCrossRefGoogle Scholar
  22. 22.
    Smolensky MH, Hermida RC, Haus E, Portaluppi F, Reinberg A. Biological rhythms, medication safety, and women’s health. J Womens Health (Larchmt). 2005;14(1):38–46.CrossRefGoogle Scholar
  23. 23.
    Sewlall S, Pillay V, Danckwerts MP, Choonara YE, Ndesendo VM, du Toit LC. A timely review of state-of-the-art chronopharmaceuticals synchronized with biological rhythms. Curr Drug Deliv. 2010;7(5):370–88.PubMedCrossRefGoogle Scholar
  24. 24.
    Smolensky MH, D’Alonzo GE. Investigative protocols for chronotherapeutics. Basic requirements and illustrative case histories. Ann N Y Acad Sci. 1991;618:465–83.PubMedCrossRefGoogle Scholar
  25. 25.
    Ohdo S. Chronopharmacology focused on biological clock. Drug Metab Pharmacokinet. 2007;22(1):3–14.PubMedCrossRefGoogle Scholar
  26. 26.
    Reinberg AE. Concepts of circadian chronopharmacology. Ann N Y Acad Sci. 1991;618:102–15.PubMedCrossRefGoogle Scholar
  27. 27.
    Bruguerolle B, Philip-joet F, Parrel M, Arnaud A. Unequal twice-daily, sustained-release theophylline dosing in chronic obstructive pulmonary disease. Chronobiol Int. 1987;4(3):381–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Hassan A, Haefeli WE. Appropriateness of timing of drug administration in electronic prescriptions. Pharm World Sci. 2010;32(2):162–71.PubMedCrossRefGoogle Scholar
  29. 29.
    Alten R, Doring G, Cutolo M, Gromnica-Ihle E, Witte S, Straub R, et al. Hypothalamus-pituitary-adrenal axis function in patients with rheumatoid arthritis treated with night time-release prednisone. J Rheumatol. 2010;37(10):2025–31.PubMedCrossRefGoogle Scholar
  30. 30.
    Asmar R, Gosse P, Quere S, Achouba A. Efficacy of morning and evening dosing of amlodipine/valsartan combination in hypertensive patients uncontrolled by 5 mg of amlodipine. Blood Press Monit. 2011;16(2):80–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Bethke TD, Huennemeyer A, Lahu G, Lemmer B. Chronopharmacology of roflumilast: a comparative pharmacokinetic study of morning versus evening administration in healthy adults. Chronobiol Int. 2010;27(9–10):1843–53.PubMedCrossRefGoogle Scholar
  32. 32.
    Glass-Marmor L, Paperna T, Galboiz Y, Miller A. Immunomodulation by chronobiologically-based glucocorticoids treatment for multiple sclerosis relapses. J Neuroimmunol. 2009;210(1–2):124–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Lee RD, Mulford D, Wu J, Atkinson SN. The effect of time-of-day dosing on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR: evidence for dosing flexibility with a dual delayed release proton pump inhibitor. Aliment Pharmacol Ther. 2010;31(9):1001–11.PubMedGoogle Scholar
  34. 34.
    Magnussen H, Verkindre C, Jack D, Jadayel D, Henley M, Woessner R, et al. Indacaterol once-daily is equally effective dosed in the evening or morning in COPD. Respir Med. 2010;104(12):1869–76.PubMedCrossRefGoogle Scholar
  35. 35.
    Malhotra BK, Crownover PH, LaBadie R, Glue P, MacDiarmid SA. The pharmacokinetic profile of fesoterodine 8 mg with daytime or nighttime dosing. Eur J Clin Pharmacol. 2010;66(2):171–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Qvortrup C, Jensen BV, Fokstuen T, Nielsen SE, Keldsen N, Glimelius B, et al. A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX(30) and chronomodulated XELOX(30) as first-line therapy in patients with advanced colorectal cancer. Ann Oncol. 2010;21(1):87–91.PubMedCrossRefGoogle Scholar
  37. 37.
    Suic SP, Laus KN, Dosen VM, Ekert M, Mandic Z, Bojic L. Comparison of evening and morning dosing of travoprost 0.004 %/timolol 0.5 % fixed combination in 6 month Period. Coll Antropol. 2010;34(3):847–52.PubMedGoogle Scholar
  38. 38.
    Suzuki K, Aizawa Y. Evaluation of dosing time-related anti-hypertensive efficacy of valsartan in patients with type 2 diabetes. Clin Exp Hypertens. 2011;33(1):56–62.PubMedCrossRefGoogle Scholar
  39. 39.
    He YL, Valencia J, Zhang Y, Schwartz SL, Ligueros-Saylan M, Foley J, et al. Hormonal and metabolic effects of morning or evening dosing of the dipeptidyl peptidase IV inhibitor vildagliptin in patients with type 2 diabetes. Br J Clin Pharmacol. 2010;70(1):34–42.PubMedCrossRefGoogle Scholar
  40. 40.
    Warnke A, Schug B, Vanderbist F, Blume H. Significance of the biopharmaceutical properties of tramadol sustained-release formulations for chronopharmacologically optimized treatment of pain from various sources. Int J Clin Pharmacol Ther. 2009;47(6):405–12.PubMedGoogle Scholar
  41. 41.
    Yoon HS, Kim SH, Kim JK, Ko SH, Ko JE, Park SJ, et al. Comparison of effects of morning versus evening administration of ezetimibe/simvastatin on serum cholesterol in patients with primary hypercholesterolemia. Ann Pharmacother. 2011;45(7–8):841–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Zetterstrom O, Dahl R, Lindqvist A, Olsson P. Comparable morning versus evening administration of once-daily mometasone furoate dry powder inhaler. Respir Med. 2008;102(10):1406–11.PubMedCrossRefGoogle Scholar
  43. 43.
    Ayala DE, Hermida RC. Sex differences in the administration-time-dependent effects of low-dose aspirin on ambulatory blood pressure in hypertensive subjects. Chronobiol Int. 2010;27(2):345–62.PubMedCrossRefGoogle Scholar
  44. 44.
    Hermida RC, Ayala DE, Mojon A, Fernandez JR. Ambulatory blood pressure control with bedtime aspirin administration in subjects with prehypertension. Am J Hypertens. 2009;22(8):896–903.PubMedCrossRefGoogle Scholar
  45. 45.
    Bolk N, Visser TJ, Nijman J, Jongste IJ, Tijssen JGP, Berghout A. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med. 2010;170(22):1996–2003.PubMedCrossRefGoogle Scholar
  46. 46.
    Hermida RC, Ayala DE, Mojon A, Chayan L, Dominguez MJ, Fontao MJ, et al. Comparison of the effects on ambulatory blood pressure of awakening versus bedtime administration of torasemide in essential hypertension. Chronobiol Int. 2008;25(6):950–70.PubMedCrossRefGoogle Scholar
  47. 47.
    Hermida RC, Ayala DE. Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing. Hypertension. 2009;54(1):40–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Hermida RC, Ayala DE, Mojon A, Fernandez JR. Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing. Am J Hypertens. 2008;21(8):948–54.PubMedCrossRefGoogle Scholar
  49. 49.
    Hermida RC, Ayala DE, Mojon A, Alonso I, Fernandez JR. Reduction of morning blood pressure surge after treatment with nifedipine GITS at bedtime, but not upon awakening, in essential hypertension. Blood Press Monit. 2009;14(4):152–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Hermida RC, Ayala DE, Chayan L, Mojon A, Fernandez JR. Administration-time-dependent effects of olmesartan on the ambulatory blood pressure of essential hypertension patients. Chronobiol Int. 2009;26(1):61–79.PubMedCrossRefGoogle Scholar
  51. 51.
    Povedano ST, Garcia De La Villa B. 24-h and nighttime blood pressures in type 2 diabetic hypertensive patients following morning or evening administration of olmesartan. J Clin Hypertens. 2009;11(8):426–31.CrossRefGoogle Scholar
  52. 52.
    Hermida RC, Ayala DE, Fontao MJ, Mojon A, Fernandez JR. Chronotherapy with valsartan/amlodipine fixed combination: improved blood pressure control of essential hypertension with bedtime dosing. Chronobiol Int. 2010;27(6):1287–303.PubMedCrossRefGoogle Scholar
  53. 53.
    Hoshino A, Nakamura T, Matsubara H. The bedtime administration ameliorates blood pressure variability and reduces urinary albumin excretion in amlodipine-olmesartan combination therapy. Clin Exp Hypertens. 2010;32(7):416–22.PubMedCrossRefGoogle Scholar
  54. 54.
    Meng Y, Zhang Z, Liang X, Wu C, Qi G. Effects of combination therapy with amlodipine and fosinopril administered at different times on blood pressure and circadian blood pressure pattern in patients with essential hypertension. Acta Cardiol. 2010;65(3):309–14.PubMedCrossRefGoogle Scholar
  55. 55.
    Zeng J, Jia M, Ran H, Tang H, Zhang Y, Zhang J, et al. Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing a multicenter, open-label randomized study. Hypertens Res. 2011;34(6):767–72.PubMedCrossRefGoogle Scholar
  56. 56.
    Konstas AG, Hollo G, Mikropoulos D, Tsironi S, Haidich AB, Embeslidis T, et al. Twenty-four-hour intraocular pressure control with bimatoprost and the bimatoprost/timolol fixed combination administered in the morning, or evening in exfoliative glaucoma. Br J Ophthalmol. 2010;94(2):209–13.PubMedCrossRefGoogle Scholar
  57. 57.
    Buttgereit F, Doering G, Schaeffler A, Witte S, Sierakowski S, Gromnica-Ihle E, et al. Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis. Ann Rheum Dis. 2010;69(7):1275–80.PubMedCrossRefGoogle Scholar
  58. 58.
    Takmaz T, Asik S, Kurkcuoglu P, Gurdal C, Can I. Comparison of intraocular pressure lowering effect of once daily morning vs evening dosing of latanoprost/timolol maleate combination. Eur J Ophthalmol. 2008;18(1):60–5.PubMedGoogle Scholar
  59. 59.
    Tharavanij T, Wongtanakarn S, Lerdvuthisopon N, Teeraaunkul S, Youngsriphithak P, Sritipsukho P. Lipid lowering efficacy between morning and evening simvastatin treatment: a randomized double-blind study. J Med Assoc Thail. 2010;93(Suppl 7):S109–13.Google Scholar
  60. 60.
    Okeahialam B, Ohihoin E, Ajuluchukwu J. Chronotherapy in Nigerian hypertensives. Ther Adv Cardiovasc Dis. 2011;5(2):113–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Almeida L, Loureiro AI, Vaz-Da-Silva M, Torrao L, Maia J, Fernandes-Lopes C, et al. Chronopharmacology of nebicapone, a new catechol-O-methyltransferase inhibitor. Curr Med Res Opin. 2010;26(5):1097–108.PubMedCrossRefGoogle Scholar
  62. 62.
    Smolensky MH. Compliance to prescription medications entails respect for treatment timing. Chronobiol Int. 2002;19(2):502–5.PubMedGoogle Scholar
  63. 63.
    Smolensky MH, Peppas NA. Chronobiology, drug delivery, and chronotherapeutics. Adv Drug Deliv Rev. 2007;59(9–10):828–51.PubMedCrossRefGoogle Scholar
  64. 64.
    Kraft M, Martin RJ. Chronobiology and chronotherapy in medicine. Dis Mon. 1995;41(8):501–75.CrossRefGoogle Scholar
  65. 65.
    Prins JM, Weverling GJ, van Ketel RJ, Speelman P. Circadian variations in serum levels and the renal toxicity of aminoglycosides in patients. Clin Pharmacol Ther. 1997;62(1):106–11.PubMedCrossRefGoogle Scholar
  66. 66.
    Ohdo S, Wang DS, Koyanagi S, Takane H, Inoue K, Aramaki H, et al. Basis for dosing time-dependent changes in the antiviral activity of interferon-alpha in mice. J Pharmacol Exp Ther. 2000;294(2):488–93.PubMedGoogle Scholar
  67. 67.
    Lund TM, Torsvik H, Falch D, Christophersen B, Skardal R, Gullestad L. Effect of morning versus evening intake of simvastatin on the serum cholesterol level in patients with coronary artery disease. Am J Cardiol. 2002;90(7):784–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Qureshi J, Amir M, Ahuja A, Baboota S, Ali J. Chronomodulated drug delivery system of salbutamol sulphate for the treatment of nocturnal asthma. Indian J Pharm Sci. 2008;70(3):351–6.PubMedCrossRefGoogle Scholar
  69. 69.
    Balan H. Bedtime versus at awakening administration of BP lowering drugs—is it the way to success? Rom J Intern Med. 2009;47(4):355–61.PubMedGoogle Scholar
  70. 70.
    Hermida RC, Ayala DE, Fontao MJ, Mojon A, Alonso I, Fernandez JR. Administration-time-dependent effects of spirapril on ambulatory blood pressure in uncomplicated essential hypertension. Chronobiol Int. 2010;27(3):560–74.PubMedCrossRefGoogle Scholar
  71. 71.
    Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care. 2011;34(6):1270–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Hermida RC, Ayala DE, Fernandez JR, Calvo C. Chronotherapy improves blood pressure control and reverts the nondipper pattern in patients with resistant hypertension. Hypertension. 2008;51(1):69–76.PubMedCrossRefGoogle Scholar
  73. 73.
    Hermida RC, Ayala DE, Mojon A, Fernandez JR. Effects of time of antihypertensive treatment on ambulatory blood pressure and clinical characteristics of subjects with resistant hypertension. Am J Hypertens. 2010;23(4):432–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010;27(8):1629–51.PubMedCrossRefGoogle Scholar
  75. 75.
    Pizzuto M, Portelli J, Serracino-Inglott A, Zarb-Adami M, Azzopardi LM. Chronopharmacology of antihypertensives. J Appl Ther Res. 2010;7(4):133–40.Google Scholar
  76. 76.
    To H, Yoshimatsu H, Tomonari M, Ida H, Tsurumoto T, Tsuji Y, et al. Methotrexate chronotherapy is effective against rheumatoid arthritis. Chronobiol Int. 2011;28(3):267–74.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Gagandeep Kaur
    • 1
    Email author
  • Craig Phillips
    • 2
  • Keith Wong
    • 2
  • Bandana Saini
    • 3
  1. 1.Room S114, Pharmacy and Bank Building A15, Faculty of PharmacyUniversity of SydneyCamperdownAustralia
  2. 2.Woolcock Institute of Medical ResearchCamperdownAustralia
  3. 3.Room S303, Pharmacy and Bank Building A15, Faculty of PharmacyUniversity of SydneyCamperdownAustralia

Personalised recommendations