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European Journal of Clinical Pharmacology

, Volume 71, Issue 8, pp 901–909 | Cite as

Clinical pharmacokinetics of melatonin: a systematic review

  • Nathja Groth HarpsøeEmail author
  • Lars Peter Holst Andersen
  • Ismail Gögenur
  • Jacob Rosenberg
Review Article

Abstract

Purpose

The aim of the review was to provide an overview of studies investigating the pharmacokinetics of exogenous melatonin in humans and if possible, to provide recommendations for clinical use.

Methods

The review was conducted in accordance to PRISMA guidelines. A systematic literature search was performed in PubMed and Embase databases. The pharmacokinetic variables included maximal plasma/serum concentration (Cmax), time to maximal plasma/serum concentration (Tmax), elimination half-life (T1/2), area-under-the-curve plasma/serum concentrations (AUC), clearance (Cl), volume of distribution (VD), and bioavailability.

Results

The literature search identified 392 records. Twenty-two studies were included in the review. Melatonin dosages varied between 0.3 and 100 mg and were administered either orally or intravenously. Cmax ranged from 72.1 (10 ml/h; 0.02 mg, IV) to 101,163 pg/ml (100 mg, oral). Tmax ranged between 15 (2 mg) and 210 min (10 mg). T1/2 ranged from 28 (0.005 mg, IV) to 126 min (4 mg, oral), whereas AUC ranged between 5400 (0.005 mg, IV) and 6.56 × 1010 pg/ml × min (1 mg, oral). Cl ranged from 0.97 (0.005 mg, IV) to 132.50 L/min (6 mg, oral), whereas VD ranged between 35 (0.005 mg, IV) and 1602 L (4 mg, oral). Bioavailability of oral melatonin ranged from 9 to 33 %. Pharmacokinetics was affected by age, caffeine, smoking, oral contraceptives, feeding status, and fluvoxamine. Critically ill patients displayed accelerated absorption and compromised elimination.

Conclusions

Despite methodological differences between the included studies, Tmax was approximately 50 min following oral immediate-release formulations of melatonin. T1/2 was 45 min in both administration routes. Cmax, AUC, Cl, and VD varied extensively between studies. Bioavailability of oral melatonin was approximately 15 %.

Keywords

Exogenous Melatonin Patients Pharmacokinetic Volunteers 

Notes

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Nathja Groth Harpsøe
    • 1
    Email author
  • Lars Peter Holst Andersen
    • 1
  • Ismail Gögenur
    • 2
  • Jacob Rosenberg
    • 1
  1. 1.Department of Surgery D, Herlev HospitalUniversity of CopenhagenHerlevDenmark
  2. 2.Department of Surgery, Køge and Roskilde HospitalUniversity of CopenhagenKøgeDenmark

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