Chronomodulated drug delivery system: A comprehensive review on the recent advances in a new sub-discipline of ‘chronopharmaceutics’

Rohit Bisht

Abstract


With the advancement in the field of chronobiology, modern drug delivery approaches have been elevated to a new concept of chronopharmacology, that is, the ability to deliver the therapeutic agent to a patient in a staggered profile.
The mammalian circadian pacemaker resides in the paired suprachiasmatic nuclei and influences a multitude of biological processes, including the sleep–wake rhythm. Clock genes are the genes that control the circadian rhythms in physiology and behavior. Twenty-four hours rhythms are demonstrated for the function of physiology and the pathophysiology of diseases. The effectiveness and toxicity of many drugs vary depending on the dosing time. Such chronopharmacological phenomena are influenced by not only the pharmacodynamics, but also the pharmacokinetics of medications.The underlying
mechanisms are associated with the 24-hour rhythms of biochemical,physiological, and behavioral processes under thecontrol of the circadian clock. New technology for delivering medications precisely in a time-modulated fashion, by bedside or ambulatory pumps, is being developed to manage human diseases. From the point of view of pharmaceutics, the
application of a biological rhythm to pharmacotherapy may be accomplished by the appropriate timing of conventionally formulated tablets and capsules, and a special drug delivery system, to synchronize the drug concentrations with the
rhythms in the disease activity. Therefore, the present article gives an overview of the dosing time-dependent alterations in the therapeutic outcome and safety of the drug. The underlying mechanisms and usefulness are introduced from the
point of view of chronopharmacology and chronotherapy.


Full Text:

PDF

References


Halberg F, Stephens AN. Susceptibility to ouabain and physiologic

circadian periodicity. Proc Minn Acad Sci 1959;27:139-43.

Albrecht U, Sun ZS, Eichele G, Lee CC. A differential response of two

putative mammalian circadian regulators, mper1 and mper2, to light.

Cell 1997;91:1055-64.

Tei H, Okamura H, Shigeyoshi Y, Fukuhara C, Ozawa K, Hirose M, et al.

Circadian oscillation of a mammalian homologue of the Drosophila

period gene. Nature 1997;389:512-6.

Takumi T, Taguchi K, Miyake S, Sakakida Y, Takashima N, Matsubara C,

et al. A light independent oscillatory gene mPer3 in mouse SCN and

OVLT. EMBO J 1998;17:4753-9.

Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP,

et al. Role of the CLOCK protein in the mammalian circadian mechanism.

Science 1998;280:1564-9.

Ikeda M, Nomura M. cDNA cloning and tissue-specific expression of a

novel basic helix–loop–helix/PAS protein (BMAL1) and identification of

alternatively spliced variants with alternative translation initiation site

usage. Biochem Biophys Res Commun 1997;233:258-64.

Sangoram AM, Saez L, Antoch MP, Gekakis N, Staknis D, Whiteley A,

et al. Mammalian circadian autoregulatory loop: A timeless ortholog

and mPER1 interact and negatively regulate CLOCKBMAL1- induced

transcription. Neuron 1998;21:1101-13.

Okamura H, Miyake S, Sumi Y, Yamaguchi S, Yasui A, Muijtjens M, et al.

Photic induction of mPer1 and mPer2 in Crydeficient mice lacking a

biological clock. Science 1999;286:2531-4.

Lowrey PL, Shimomura K, Antoch MP, Yamazaks S, Zemenides PD, Ralph MR, et al. Positional systemic cloning and functional characterization

of the mammalian circadian mutation tau. Science 2000;288:483-92.

Tei H, Okamura H, Shigeyoshi Y, Fukuhara C, Ozawa K, Hirose M, et al.

Circadian oscillation of a mammalian homologue of the Drosophila

period gene. Nature 1997;389:512-6.

Bussemer T, Peppas NA, Bodmeier R. Evaluation of the swelling,

hydration and rupturing properties of the swelling layer of a rupturable

pulsatile drug delivery system. Eur J Pharm. Biopharm 2003;56:261-70.

Martin RJ, Banks-Schlegel S. Chronobiology of asthma. Am J Respir Crit Care Med 1998;158:1002-7.

Bruguerolle B, Labrecque G. Rhythmic pattern in pain and their

chronotherapy. Adv Drug Deliv. Rev 2007;59:883-95.

Morta R, Jose L, Vila J. Design of new multiparticulate sysmem for

potential site-specific and controlled drug delivery to the colonic

region. J Contr Rel 1998;55:67-77.

Richard JM, Susan BS. Chronobiology of asthma. Am J Resp Crit Care

Med. 1998;158:1002-7. Available from: http://www.atsjournals.org.[Last

accessed on 2010 Dec 02].

Sangalli ME, Maroni A, Zema L, Busetti C, Giordano F, Gazzaniga A.

In vitro and in vivo evaluation of an oral system for time and/or site-

specific drug delivery. J Control Release 2001;73:103-10.

Mohamad A, Dashevsky A. pH-independent pulsatile drug delivery

system based on hard gelatin capsules and coated with aqueous

dispersion Aquacoat ECD. Eur J Pharm Biopharm 2006;64:173-9.

Gazzaniga A, Maroni A, Sangalli ME, Zema L. Time-controlled oral delivery systems for colon targeting. Exp Opin. Drug Deliv 2006;5:583-97.

Khan Z, Pillay V, Choonara YE, du Toit LC. Drug delivery technologies

for chronotherapeutic applications. Pharm Dev Technol 2009;14:602-12.

Saigal N, Baboota S, Ahuja A, Ali J. Multiple pulse drug delivery systems: Setting a new paradigm for infectious disease therapy. Expert Opin Drug Deliv 2009;6:441-52.

Sawada T, Sako K, Yoshihara K, Nakamura K, Yokohama S, Hayashi M.

Timed-release formulation to avoid drug–drug interaction between

diltiazem and midazolam. J Pharm Sci 2003;92:790-7.

Stevens H, Chariot M, Arnold F, Lewis G. Sustained release

pharmaceutical composition of diltiazem. U.S. patent 5112621, May

, 1992.

Halberg F. Chronobiology. Annu Rev Physiol 1969;31:675-725.

Reinberg A, Halberg F. Circadian chronopharmacology. Annu Rev

Pharmacol 1971;11:455-92.

Smolensky MH, Labrecque G. Chronotherapeutics. Pharm News

;4:10-6.

Ohdo S. Changes in toxicity and effectiveness with timing of drug

administration. Implications for drug safety. Drug Safety 2003;26:999-

Ohdo S. Chronopharmaceutics: Pharmaceutics focused on biological

rhythm. Biol Pharm Bull 2010;33:159-67.

Ohdo S. Chronopharmacology focused on biological clock. Drug Metab

Pharmacokinet 2007; 22:3-14.

Moore JG, Englert E Jr. Circadian rhythm of gastric acid secretion in

man. Nature 1970;226:1261-2.

Bloom PB, Filion RD, Stunkard AJ, Fox S, Stellar E. Gastric and duodenal

motility, food intake and hunger measured in man during a 24-h period.

Am J Dig Dis 1970;15:719-25.

Belanger P, Bruguerolle B, Labrecque G. Rhythms in pharmacokinetics:

Absorption, distribution, metabolism and excretion. In: Redfern PH,

Lemmer B, editors. Physiology and Pharmacology of Biological Rhythms.

Heidelberg: Springer-Verlag; 1997. p. 177-204.

Labrecque G, Belanger P. Biological rhythms in the absorption,

distribution, metabolism and excretion of drugs. Pharmacol Ther

;52:95-107.

Reinberg A, Smolensky M. Circadian changes of drug disposition in

man. Clin Pharmacokinet 1982;7:401-20.

Bruguerolle B. Chronopharmacokinetics: Current status. Clin

Pharmacokinet 1998;35:83-94.

Labrecque G, Belanger P. Biological rhythms in the absorption,

distribution, metabolism and excretion of drugs. Pharmacol Ther

;52:95-107.

Anderson NH, Devlin AM, Graham D, Morton JJ, Hamilton CA, Reid JL,

et al. Telemetry for cardiovascular monitoring in a pharmacological

study: New approaches to data analysis. Hypertension 1999;33:248-55.

Pleschka K, Heinrich A, Witte K, Lemmer B. Diurnal and seasonal

changes in sympathetic signal transduction in cardiac ventricles of

European hamsters. Am J Physiol 1996;270:304-9.

Bruguerolle B, Arnaud C, Levi F, Focan C, Touitou Y, Bouvenot G.

Physiopathological alterations of alpha 1 acid glycoprotein temporal

variations: Implications for chronopharmacology. In: Baumann P, C.B.

Chronobiol Int 2008; 25(1):1-15

Feuers RJ, Scheving LE. Chronobiology of hepatic enzymes. Ann Rev

Chronopharmacol 1988;4:209-54.

Belanger PM, Labrecque G. Temporal aspects of drug metabolism. In:

Lemmer B, editor. Chronopharmacology: Cellular and Biochemical

Interactions. Basel: Marcel Dekker; 1991. p. 15-34.

Ohno M, Yamaguchi I, Ito T, Saiki K, Yamamoto I, Azuma J.

Physiopathological alterations of alpha 1 acid glycoprotein temporal

variations: Implications for chronopharmacology. Circadian variation of

the urinary 6 beta-hydroxycortisol to cortisol ratio that would reflect

hepatic CYP3A activity. Eur J Clin Pharmacol 2000;55:861-5.

Cambar J, Cal JC, Tranchot J. Renal excretion: Rhythms in physiology and

pathology. In: Touitou Y, Physiopathological alterations of alpha 1 acid

glycoprotein temporal variations: Implications for chronopharmacology.

Haus E, editors. Biological Rhythms in Clinical and Laboratory Medicine.

Paris: Springer-Verlag; 1992. p. 470-82.

Detli L, Spring P. Diurnal variations in the elimination rate of

sulphonamide in man. Helv Med Acta 1966;4:921-926.

Sydenham T. The Works of Thomas Sydenham. Translated from the Latin

by Lathan RG, editor. Vol. 2. London, Sydenhm socity. 1850. p. 124.

Harris MD, Siegel LB, Alloway JA. Gout and hyperuricemia Am Fam

Phys 1999;59:925-34.

Rigas B, Torosis J, McDougall CJ, Vener KJ, Spiro HM. The circadian

rhythm of biliary colic. J Clin Gastroenterol 1990;12:409-14.

Moore JG, Halberg F. Circadian rhythm of gastric acid secretion in

active duodenal ulcer: Chronobiological statistical characteristics and

comparison of acid secretory and plasma gastrin patterns in healthy and

post-vagotomy and pyloroplasty patients. Chronobiol Int 1987;4:101-10.

Cugini P, Di Palma L, Battisti P, Leone G, Materia E, Parenzi A, et al.

circadian and infradian periodicity of some cardiovascular emergencies.

Am J Cardiol. 1990;66:240-243.

Kroetz CO, Ein biologiescher 24-Studen-Rhythmus des Blutkreislaufs

bei Gesundheit und bei Herzschivache zugleich ein Beitrag zur

tageszeitlichen Haufung einiger akuter Kreislaufstorunge. Munch Med

Wochenschr. 1940;87:314-7.

Turner-Warwick M. Epidemiology of nocturnal asthma. Am J Med

;85:6-8.

Bateman JR, Clark SW. Sudden death in asthma. Thorax 1979;34:40-4.

Kelmanson IA. Circadian variation of the frequency of sudden infant

death syndrome and of sudden death from life-threatening conditions

in infants. Chronobiologia 1991;18:181-6.

Reinberg AE, Gervais P, Levi F, Smolensky M, Del Cerro L, Ugolini C.

Circadian and circannual rhythms of allergic rhinitis: An epidemiologic

study involving chronobiologic methods. J Allergy Clin Immunol

;81:51-62.

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;95:1084-96.

Kowanko IC, Knapp MS, Pownall R, Swannell AJ. Domiciliary self

measurement in rheumatoid arthritis and the demonstration of

circadian rhythmicity. Ann Rheum Dis 1982;41:453-5.

Solomon GD. Circadian rhythms and migraine. Clevel Clin J Med

;59:326-9.

Dexter JD, Weizman ED. The relationship between nocturnal headaches

to sleep stage patterns. Neurology 1970;20:513-8.

Rocco MB, Barry J, Campbell S, Nabel E, Cook EF, Goldman L, et al,

Circadian variation of transient myocardial ischemia in patients with

coronary artery disease. Circulation 1987;75:395-400.

Mulcahy D, Keegan J, Cunningham D, Quyyumi A, Crean P, Park A, et al,Circadian variation of total ischemic burden and its alteration with

anti-anginal agents. Lancet 1998;2:755-9.

Behrens S, Ehlers C, Brüggemann T, Ziss W, Dissmann R, Galecka M, et al.Modification of the circadian pattern of ventricular tachyarrthythmias

by beta-blocker therapy. Clin Cardiol1997;20:253-7.

Goldstein S, Zoble RG, Akiyama T, Cohen JD, Lancaster S, Liebson

PR, et al, Relation of circadian ventricular ectopic activity to cardiac

mortality CAST Investigators. Am J Cardiol 1996;78:881-5.

Venditti FJ Jr, John RM, Hull M, Tofler GH, Shahian DM, Martin DT.

Circadian variation in defibrillation energy requirements. Circulation

;94:1607-12.

Cohen MC, Rohtla KM, Lavery CE, Muller JE, Mittleman MA. Meta

analysis of the morning excess of acute myocardial infarction and

sudden cardiac death. Am J Cardiol 1997;79:1512-6.

Elliott WJ. Circadian variation in the timing of stoke onset. A meta

analysis. Stroke 1998;29:992-6.

Gallerani M, Manfredini R, Ricci L, Grandi E, Cappato R, Calò G. Sudden

death from pulmonary thromboembolism: Chronobiological aspects.

Eur Heart J 1992;6:305-23.

Gallerani M, Manfredini R, Fersini C. Chronoepidemiology in human

disease. Ann Inst Super Sanita 1993;29:569-79.

Portaluppi F, Manfredini R, Fersini C. From a static to a dynamic concept

of risk: The circadian epidemiology of cardiovascular risk. Chronobiol

Int 1999;16:33-50.

Wehr TA. Circadian rhythm disturbances in depression and mania. In:

Brown FM, Graeber RC, editors. Rhythmic Aspects of Behavior. New

Jerey. Lawrence Erlbaum Ass; 1982. p. 399-428.

Bellamy N, Sothern RB, Campbell J. Rhythmic variations in pain

perception in osteoarthritis of the knee. J Rheumatol 1990;

:364-72.

Folkard S. Diurnal variation and individual differences in the perception

of intractable pain. J Psychosom Res 1976;20:289-304.

Manfredini R, Gallerani M, Salmi R, Calò G, Pasin M, Bigoni M. Circadian

variation in the time of onset of acute intestinal bleeding. J Emerg

Med 1994;12:5-9.

Svanes C, Sothern RB, Sorbye H. Rhythmic patterns in incidence of

peptic ulcer perforation over 5.5 decades in Norway. Chronobiol Int

;15:241-264.

Langdon-Down M, Brain WR. Time of day in relation to convulsion in

epilepsy. Lancet 1929;12:1029-1032.

Baxil CW, Walczak TS. Effects of sleep and sleep stage on epileptic and

nonepileptic seizures. Epilepsia 1997;38:56-62.

Ohdo S, Koyanagi S, Suyama H, Higuchi S, Aramaki H. Changing the

dosing schedule minimizes the disruptive effects of interferon on clock

function. Nat Med 2001;7:356-60.

Youan BC. Chronopharmaceutics: Gimmick or clinically relevant

approach to drug delivery?. J Control Rel 2004;98:337-53.

Jao F, Wong P, Huynh H, McChesney K, Wat P. United States: Alza

Corporation. 1992. p. 17.

Verma R, Sanjay G. Current status of drug delivery technologies and

future directions. Pharm Technol 2001;25:1-14.

Leslie S. Euroceltique, SA, United States: 1982. p. 20.

Leslie S. The Contin delivery system: Dosing considerations. J Allergy

Clin Immunol 1986;78:768-73.

Arkinstall WW. Review of the North American experience with evening

administration of Uniphyl tablets, a once-daily theophylline preparation,

in the treatment of nocturnal asthma. Am J Med 1988;85:60-3.

Percel P, Vishnupad K, Venkatesh GM. Timed pulsatile drug delivery

systems. US Patent 6,627,223.

FDA. In: Electronic Orange Book. Washington, DC: Electronic Orange

Book; 2003.

Youan BC. Overview of chronopharmaceutics. In: Youan BC, Editor.

Chronopharmaceutics: Science and Technology for Biological Rhythm

Guided Therapy and Prevention of Diseases. Hoboken, NJ: John Wiley

and Sons, Inc; 2009.

Prisant LM, Devane JG, Butler J. A steady-state evaluation of the

bioavailability of chronopharmaceutic oral drug absorption system

verapamil PM after night time dosing versus immediate-acting

verapamil dosed every 8 h. Am J Ther 2000;7:345-51.

Panoz D, Geoghegan E. Elan Corporation, United States, 1989. p. 49.

Conte U, Maggi L. Modulation of the dissolution profiles from

Geomatrix® multilayer matrix tablets containing drugs of different

solubility. Biomoterials 1996;17:889-96.

Katstra WE, Palazzolo RD, Rowe CW, Giritlioglu B, Teung P, et al, Oral

dosage forms fabricated by three dimensional printing. J Control

Release 2000;66:1-9.

Rowe CW, Katstra WE, Palazzolo RD, Giritlioglu B, Teung P, et al,

Multimechanism oral dosage forms fabricated by three dimensional

printing. J Control Release 2000;66:11-7.

Monkhouse D, Yoo J, Sherwood J, Cima M, Bornancini E. Therics. United

States, 2003. p. 19.

Staniforth JN, Baichwal AR, TIMERx®: Novel polysaccharide composites

for controlled/programmed release of drugs in the gastrointestinal

tract. Expert Opin Drug Deliv 2005;2:587-95.

Horter D, Dressman JB. Influence of physicochemical properties on

dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev

;46:75-87.

Mahey R, Bersot T. Drug therapy for hypercholesterolemia and

dyslipidemia. In: Hardman J, Limbird L, Gilman A, editors. Goodman

and Gilman's The Pharmacological Basis of Therapeutics. New York:

McGraw-Hill; 2001.

Santini JT Jr, Cima MJ, Langer R. A controlled-release microchip. Nature

;397:335-8.

Santini JT Jr, Richards AC, Scheidt R, Cima MJ, Langer R. Microchips

as controlled drug-delivery devices. Angew Chem Int Ed Engl

;39:2396-407.

Sershen S, West J. Implantable, polymeric systems for modulated drug

delivery. Adv Drug Deliv 2002;54:1225-35.

Levi F, Zidani R, Misset JL. Randomised multicentre trial of chronotherapy

with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal

cancer. International Organization for Cancer Chronotherapy. Lancet

;350:681-6.

Remeling R, Hrushesky WJ. Circadian patterning of continuous

floxuridine infusion reduces toxicity and allows higher dose intensity

in patients with widespread cancer. J Clin Oncol 1989;7:1710-9.

Tzannis ST, Hrushesky WJ, Wood PA, Przybycien TM. Irreversible

inactivation of interleukin 2 in a pump-based delivery environment.

Proc Natl Acad Sci USA 1996;93:5460-5.




DOI: http://dx.doi.org/10.22377/ajp.v5i1.77

Refbacks

  • There are currently no refbacks.