Pharmacokinetics of Alternative Administration Routes of Melatonin: A Systematic Review

Drug Res (Stuttg). 2016 Apr;66(4):169-73. doi: 10.1055/s-0035-1565083. Epub 2015 Oct 29.


Background: Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin.

Methods: A systematic literature search was performed and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration routes except oral and intravenous.

Results: 10 studies were included in the review. Intranasal administration exhibited a quick absorption rate and high bioavailability. Transdermal administration displayed a variable absorption rate and possible deposition of melatonin in the skin. Oral transmucosal administration of melatonin exhibited a high plasma concentration compared to oral administration. Subcutaneous injection of melatonin displayed a rapid absorption rate compared to oral administration.

Conclusion: Intranasal administration of melatonin has a large potential, and more research in humans is warranted. Transdermal application of melatonin has a possible use in a local application, due to slow absorption and deposition in the skin. Oral transmucosal administration may potentially be a clinically relevant due to avoiding first-pass metabolism. Subcutaneous injection of melatonin did not document any advantages compared to other administration routes.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Administration, Cutaneous
  • Administration, Intranasal
  • Administration, Mucosal
  • Administration, Oral
  • Animals
  • Biological Availability
  • Humans
  • Injections, Subcutaneous
  • Melatonin / administration & dosage*
  • Melatonin / pharmacokinetics*


  • Melatonin