A Randomized, Crossover, Pharmacokinetics Evaluation of a Novel Continuous Release and Absorption Melatonin Formulation

Prim Care Companion CNS Disord. 2019 Aug 1;21(4):19m02450. doi: 10.4088/PCC.19m02450.

Abstract

Objective: To evaluate the pharmacokinetic and safety profile of a novel continuous release and absorption melatonin (CRA-melatonin) compared with an immediate-release melatonin (IR-melatonin) product.

Methods: The REM Absorption Kinetics Trial (REMAKT), an open-label, single-center, randomized, single-dose, 2-way crossover trial, compared the pharmacokinetic and safety profile of CRA-melatonin (5 mg) with IR-melatonin (5 mg) in healthy adult volunteers. The study was conducted from March 18, 2016, to April 20, 2016.

Results: Ten subjects completed REMAKT. Plasma melatonin levels exceeded the targeted maintenance threshold level of 1,000 pg/mL for a median of 6.7 hours for CRA-melatonin compared with 3.7 hours for IR-melatonin. The median Cmax was 4,690 pg/mL for CRA-melatonin and 23,352 pg/mL for IR-melatonin. In REMAKT, there were no treatment-emergent adverse events reported in the CRA-melatonin arm. Five treatment-emergent adverse events occurred with IR-melatonin.

Conclusions: The novel, well-tolerated CRA-melatonin was shown to achieve quick release and then continuous release and absorption of melatonin for up to 7 hours, making it a significant advancement in the pharmacokinetic release profile of exogenous melatonin delivery and, therefore, an important potential consideration as a baseline therapy for sleep.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Central Nervous System Depressants / administration & dosage*
  • Central Nervous System Depressants / adverse effects
  • Central Nervous System Depressants / pharmacokinetics*
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Female
  • Humans
  • Male
  • Melatonin / administration & dosage*
  • Melatonin / adverse effects
  • Melatonin / pharmacokinetics*
  • Young Adult

Substances

  • Central Nervous System Depressants
  • Delayed-Action Preparations
  • Melatonin