Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

Lars Andersen and colleagues created a study to examine the pharmacokinetics of melatonin administered orally, and intravenously.  This was a cohort crossover study in which volunteers were given either 10 mg melatonin orally or 10 mg of intravenous melatonin on two occasions.  Twelve male volunteers with an average age of 27 years old and an average BMI of 23.2 kg/m2.

Some pharmacokinetic parameters were measured for both oral and intravenous routes including half-life, area under curve (AUC), and volume of distribution for intravenous.  The half-life for the oral route was found to be 53.7 minutes, and 39.4 minutes for the intravenous method.  The AUC for the oral melatonin 281,538.3 pg*mL-1*min, and the intravenous melatonin was found to have an AUC 14,179,767.6 pg*mL-1*min.  The volume of distribution was found to be 1.2 L/kg.

The study concluded that the oral melatonin had a very low bioavailability of about 3%.  They commented how other studies they found ranged from 9-33% availability.  The one similarity between the studies they reviewed and this study was that there was high variability between patients.  The low availability was due to the extensive first pass effect from the liver.  The intravenous melatonin was found to be have first order elimination kinetics.  The parameters found with the intravenous study fell within the limits that were predicted based on previous studies.

Studies like this one are very important to help optimize a medications effects.  When examining pharmacokinetic effects do you think that it is important to include both sexes in the volunteer pool?  How does the variable bioavailability affect the results of each patient that takes oral melatonin?

BMC Pharmacol Toxicol. 2016;17:8. 

Sleep, Shift Work and the Effects of Pharmaceutical Interventions

In the United States, 29% of employed persons do not work during regular business hours, or the “day shift”. These employees have jobs requiring shift work, which is commonly associated with reduced sleep, a more difficult time sleeping during the day, and a decrease in their alertness while working their night shifts. There have been a few studies that show melatonin is associated with an average of 24 minutes more of daytime sleep after a person works a night shift, and increases nighttime sleep by 17 minutes, however no dose-response association was found. In addition, there was no association with melatonin and the time required to fall asleep. Hypnotic medications were also studied, but there was no association with a longer period of daytime sleep.


The study also looked at medications that increase alertness, such as Armodafinil. If taken before a night shift, the person experienced less sleepiness by 1 point on the Karolinska Sleepiness Scale, and an increase in alertness in a simple reaction time test. However, some side effects that were seen were headaches and nausea. People who drank caffeine and took a nap before working a night shift also had decreased sleepiness and an increased alertness, but this evidence is rated as “low-quality”.

JAMA. 2015;313(9):961-962

I chose this article because my dad worked shift work as I was growing up and I could see the effects it had on his body and his health. He always had difficulty sleeping during the day, and when his shifts switched from night to day, he had difficulty readjusting to our “normal” sleep patterns. Looking back, I wonder if he ever tried any of these medications to help him sleep better during the days or to help him stay alert while at work. If I were to make a recommendation to him or to anyone, I would want there to be greater studies done on the effects of these medications so that the evidence is not as low-quality. Until that is done, though, what would you do if a patient working shift work asked you what could help with their sleep health? What additional health problems could arise from shift work that we should be aware of and advise patients about?

Melatonin Supplementation for Children With Atopic Dermatitis and Sleep Disturbance

Difficulty sleeping is commonplace for children with atopic dermatitis, a condition similar to eczema that causes itchy inflammation of the skin. It has been found that children suffering from AD have decreased levels of nighttime melatonin. Because melatonin has both sleep-inducing and anti-inflammatory properties, the researchers in this study hypothesized that melatonin may be an effective treatment for pediatric patients suffering from AD.

The researchers used a randomized, double blind, placebo-controlled study involving patients aged 1-18 who had AD affecting at least 5% of their total body surface area. patients received either 3mg daily of melatonin or placebo for four weeks. The primary outcome of AD severity was measured using the SCORAD index, and the secondary outcome of sleep impact was measured using actigraphy and polysomnography, as well as urinalysis of sulfatoxymelatonin, the byproduct of melatonin metabolism.

After treatment, the SCORAD mean score dropped by 9.1, and the sleep-onset time dropped by 21.4 minutes on average. Importantly, no adverse effects were reported during the trial.

This study is interesting for patients looking for an OTC solution to both atopic dermatitis as well as sleep issues. The fact that no adverse events occured helps to support the conclusion that melatonin is not only an effective and cheaper solution to two issues as once, but it is also a safe solution in the pediatric population. This knowledge will be useful for us to know in the future, as over 3 million cases of AD are diagnosed annually(Source: Mayo Clinic)