Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study

Giovanni Mistraletti, Rita Paroni, Michele Umbrello, Bedrana Moro Salihovic, Silvia Coppola, Sara Froio, Elena Finati, Paolo Gasco, Adriana Savoca, Davide Manca, Davide Chiumello, Russel J Reiter, Gaetano Iapichino

Research output: Contribution to journalArticle

Abstract

Background and objectives: Critically ill patients present reduced endogenous melatonin blood levels, and they might benefit from its exogenous supplementation. The aim of this research was to evaluate the feasibility of different routes of administration and drug formulations of melatonin. The efficiency of absorption was assessed as well as the adequacy in achieving and maintaining the physiological nocturnal blood peak. Methods: Twenty-one high-risk critically ill patients were randomly assigned to receive melatonin either: (a) per os, as a standard tablet (ST-OS), (b) per os, as a suspension in solid lipid nanoparticles (SLN-OS) or c) transdermal (TD), by applying a jellified melatonin microemulsion (μE) on the skin (μE-TD). SLN-OS and μE-TD were lipid-based colloidal systems. The endogenous melatonin blood values were observed for 24 hours; subsequently, melatonin 3 mg was administered and pharmacokinetics was studied for 24 hours further. Results: In both groups that received ST-OS and SLN-OS, the median time-to-peak blood concentration was 0.5 hours; however, the area under the curve (AUC) after administration of SLN-OS was significantly higher than after ST-OS (157386 [65732-193653] vs 44441 [22319-90705] pg/mL*hours, P = 0.048). μE-TD presented a delayed time-to-peak blood concentration (4 hours), a lower bioavailability (AUC: 3142 [1344-14573] pg/mL*hours) and reached pharmacological peak concentration (388 [132-1583] pg/mL). Conclusions: SLN-melatonin enterally administered offers favourable pharmacokinetics in critically ill patients, with higher bioavailability with respect to the standard formulation; μE-TD provided effective pharmacological blood levels, with a time-concentration profile more similar to the physiological melatonin pattern.

Original languageEnglish (US)
JournalClinical Endocrinology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Melatonin
Critical Illness
Pharmacokinetics
Nanoparticles
Lipids
Biological Availability
Area Under Curve
Pharmacology
Drug Compounding
Tablets
Suspensions
Skin
Research

Keywords

  • critically ill patients
  • lipid nanovector encapsulation
  • melatonin
  • microemulsion
  • transdermal absorption

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Mistraletti, G., Paroni, R., Umbrello, M., Moro Salihovic, B., Coppola, S., Froio, S., ... Iapichino, G. (2019). Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study. Clinical Endocrinology. https://doi.org/10.1111/cen.13993

Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study. / Mistraletti, Giovanni; Paroni, Rita; Umbrello, Michele; Moro Salihovic, Bedrana; Coppola, Silvia; Froio, Sara; Finati, Elena; Gasco, Paolo; Savoca, Adriana; Manca, Davide; Chiumello, Davide; Reiter, Russel J; Iapichino, Gaetano.

In: Clinical Endocrinology, 01.01.2019.

Research output: Contribution to journalArticle

Mistraletti, G, Paroni, R, Umbrello, M, Moro Salihovic, B, Coppola, S, Froio, S, Finati, E, Gasco, P, Savoca, A, Manca, D, Chiumello, D, Reiter, RJ & Iapichino, G 2019, 'Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study', Clinical Endocrinology. https://doi.org/10.1111/cen.13993
Mistraletti, Giovanni ; Paroni, Rita ; Umbrello, Michele ; Moro Salihovic, Bedrana ; Coppola, Silvia ; Froio, Sara ; Finati, Elena ; Gasco, Paolo ; Savoca, Adriana ; Manca, Davide ; Chiumello, Davide ; Reiter, Russel J ; Iapichino, Gaetano. / Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study. In: Clinical Endocrinology. 2019.
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AU - Mistraletti, Giovanni

AU - Paroni, Rita

AU - Umbrello, Michele

AU - Moro Salihovic, Bedrana

AU - Coppola, Silvia

AU - Froio, Sara

AU - Finati, Elena

AU - Gasco, Paolo

AU - Savoca, Adriana

AU - Manca, Davide

AU - Chiumello, Davide

AU - Reiter, Russel J

AU - Iapichino, Gaetano

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