nach oben

Clinical Pharmacokinetics

Erschienen in:

21.03.2016 | Current Opinion

Pharmacokinetics of Melatonin: The Missing Link in Clinical Efficacy?

verfasst von: Lars Peter Holst Andersen, Ismail Gögenur, Jacob Rosenberg, Russel J. Reiter

Erschienen in: Clinical Pharmacokinetics | Ausgabe 9/2016

Einloggen, um Zugang zu erhalten

Abstract

Despite widespread clinical application of melatonin, several unanswered questions remain regarding the pharmacokinetics of this drug. This lack of knowledge may contribute to the inconsistency of results in previous clinical studies. Currently, a t _max value of 30–45 min and a t _{½elimination} of 45 min are well established. Several questions relate to what constitutes a clinically effective plasma concentration, the choice of ideal administration route, and the optimal method of analysis. Furthermore, investigations of melatonin metabolites in humans are urgently needed in order to characterize their biological functions and the metabolic fates of these derivatives. Finally, pharmacokinetics in patients should be investigated further in order to reduce the risk of potential adverse effects, such as daytime sleepiness or unintended sedation.

Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, et al. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005;9:41–50.CrossRefPubMed

Grossman E, Laudon M, Yalcin R, Zengil H, Peleg E, Sharabi Y, et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006;119:898–902.CrossRefPubMed

Koziróg M, Poliwczak AR, Duchnowicz P, Koter-Michalak M, Sikora J, Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011;50:261–6.CrossRefPubMed

De Matos Cavalcante AG, de Bruin PF, de Bruin VM, Nunes DM, Pereira ED, Cavalcante MM, et al. Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study. J Pineal Res. 2012;53:238–44.CrossRefPubMed

Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut. 2005;54:1402–7.CrossRefPubMedPubMedCentral

Andersen LPH, Werner MU, Rosenberg J, Gögenur I. A systematic review of peri-operative melatonin. Anaesthesia. 2014;69:1163–71.CrossRefPubMed

Gögenur I, Kücükakin B, Panduro Jensen L, Reiter RJ, Rosenberg J. Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair: a randomized, placebo-controlled, clinical trial. J Pineal Res. 2014;57:10–5.CrossRefPubMed

Gitto E, Romeo C, Reiter RJ, Impellizzeri P, Pesce S, Basile M, et al. Melatonin reduces oxidative stress in surgical neonates. J Pediatr Surg. 2004;39:184–9.CrossRefPubMed

Gitto E, Karbownik M, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P, et al. Effects of melatonin treatment in septic newborns. Pediatr Res. 2001;50:756–60.CrossRefPubMed

10.

Bellapart J, Boots R. Potential use of melatonin in sleep and delirium in the critically ill. Br J Anaesth. 2012;108:572–80.CrossRefPubMed

11.

Srinivasan V, Pandi-Perumal SR, Trahkt I, Spence DW, Poeggeler B, Hardeland R, et al. Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci. 2009;119:821–46.CrossRefPubMed

12.

Srinivasan V, Pandi-Perumal SR, Spence DW, Kato H, Cardinali DP. Melatonin in septic shock: some recent concepts. J Crit Care. 2010;25(656):e1–6.PubMed

13.

Garaulet M, Gómez-Abellán P, Rubio-Sastre P, Madrid JA, Saxena R, Scheer FA. Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans. Metabolism. 2015;64:1650–7.CrossRefPubMed

14.

Arendt J, Skene DJ. Melatonin as a chronobiotic. Sleep Med Rev. 2005;9:25–39.CrossRefPubMed

15.

Andersen LPH, Rosenberg J, Gögenur I. Perioperative melatonin: not ready for prime time. Br J Anaesth. 2014;112:7–8.CrossRefPubMed

16.

Harpsøe NG, Andersen LPH, Gögenur I, Rosenberg J. Clinical pharmacokinetics of melatonin: a systematic review. Eur J Clin Pharmacol. 2015;71:901–9.CrossRefPubMed

17.

Cavallo A, Ritschel WA. Pharmacokinetics of melatonin in human sexual maturation. J Clin Endocrinol Metab. 1996;81:1882–6.PubMed

18.

Bourne RS, Mills GH, Minelli C. Melatonin therapy to improve nocturnal sleep in critically ill patients: encouraging results from a small randomised controlled trial. Crit Care. 2008;12:R52.CrossRefPubMedPubMedCentral

19.

Di WL, Kadva A, Johnston A, Silman R. Variable bioavailability of oral melatonin. N Engl J Med. 1997;336:1028–9.CrossRefPubMed

20.

Andersen LP, Werner MU, Rosenkilde MM, Harpsøe NG, Fuglsang H, Rosenberg J, et al. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers. BMC Pharmacol Toxicol. 2016;17:8.CrossRefPubMedPubMedCentral

21.

Härtter S, Grözinger M, Weigmann H, Röschke J, Hiemke C. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther. 2000;67:1–6.CrossRefPubMed

22.

Härtter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine K. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br J Clin Pharmacol. 2003;56:679–82.CrossRefPubMedPubMedCentral

23.

Hilli J, Korhonen T, Turpeinen M, Hokkanen J, Mattila S, Laine K. The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C > A polymorphism. J Clin Pharmacol. 2008;48:986–94.CrossRefPubMed

24.

Lane EA, Moss HB. Pharmacokinetics of melatonin in man: first pass hepatic metabolism. J Clin Endocrinol Metab. 1985;61:1214–6.CrossRefPubMed

25.

Stefani LC, Muller S, Torres IL, Razzolini B, Rozisky JR, Fregni F, et al. A phase II, randomized, double-blind, placebo controlled, dose-response trial of the melatonin effect on the pain threshold of healthy subjects. PLoS One. 2013;8:e74107.CrossRefPubMedPubMedCentral

26.

Yaprak M, Altun A, Vardar A, Aktoz M, Ciftci S, Ozbay G. Decreased nocturnal synthesis of melatonin in patients with coronary artery disease. Int J Cardiol. 2003;89:103–7.CrossRefPubMed

27.

Hikichi T, Tateda N, Miura T. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy. Clin Ophthalmol. 2011;5:655–60.CrossRefPubMedPubMedCentral

28.

Schernhammer ES, Hankinsin SE. Urinary melatonin levels postmenopausal breast cancer risk in the nurses’ health study cohort. Cancer Epidemiol Biomark Prev. 2009;18:74–9.CrossRef

29.

Galano A, Tan DX, Reiter RJ. On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK. J Pineal Res. 2013;54:245–57.CrossRefPubMed

30.

Mistraletti G, Sabbatini G, Taverna M, Figini MA, Umbrello M, Magni P, et al. Pharmacokinetics of orally administered melatonin in critically ill patients. J Pineal Res. 2010;48:142–7.CrossRefPubMed

31.

Bellapart J, Roberts JA, Appadurai V, Wallis SC, Nuñez-Nuñez M, Boots RJ. Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients. Clin Chem Lab Med. 2016;54:467–72.CrossRefPubMed

32.

Gooneratne NS, Edwards AYZ, Zhou C, Cuellar N, Grandner MA, Barrett JS. Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults. J Pineal Res. 2012;52:437–45.CrossRefPubMedPubMedCentral

33.

Reiter R, Tan DX, Zhou Z, Cruz M, Fuentes-Broto L, Galano A. Phytomelatonin: assisting plants to survive and thrive. Molecules. 2015;20:7396–437.CrossRefPubMed

34.

Tan DX, Zanghi BM, Manchester LC, Reiter RJ. Melatonin identified in meats and other food stuffs: potentially nutritional impact. J Pineal Res. 2014;57:213–8.CrossRefPubMed

35.

Ursing C, von Bahr C, Brismar K, Röjdmark S. Influence of cigarette smoking on melatonin levels in man. Eur J Clin Pharmacol. 2005;61:197–201.CrossRefPubMed

Titel: Pharmacokinetics of Melatonin: The Missing Link in Clinical Efficacy?
verfasst von: Lars Peter Holst Andersen
Ismail Gögenur
Jacob Rosenberg
Russel J. Reiter
Publikationsdatum: 21.03.2016
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 9/2016
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-016-0386-3

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2016

Dose- and Formulation-Dependent Non-Linear Pharmacokinetic Model of Paritaprevir, a Protease Inhibitor for the Treatment of Hepatitis C Virus Infection: Combined Analysis from 12 Phase I Studies

Effect of Single Nucleotide Polymorphisms in the Xenobiotic-sensing Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Toxicity of Irinotecan in Colorectal Cancer Patients

Population Pharmacokinetics of Edoxaban in Patients with Non-Valvular Atrial Fibrillation in the ENGAGE AF-TIMI 48 Study, a Phase III Clinical Trial

Development of Romiplostim for Treatment of Primary Immune Thrombocytopenia From a Pharmacokinetic and Pharmacodynamic Perspective

Cellular Uptake of Glucocerebrosidase in Gaucher Patients Receiving Enzyme Replacement Treatment

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children