Melatonin is a naturally occurring hormone produced primarily by the pineal gland, a small endocrine gland in the brain. It regulates the body’s sleep-wake cycles, or circadian rhythm, by signaling the onset of darkness. Understanding how melatonin moves through the body, from entry to elimination, provides insight into its effects and influencing factors.
Understanding Pharmacokinetics
Pharmacokinetics describes how the body interacts with a substance, from administration to elimination. This process is summarized by ADME: Absorption, Distribution, Metabolism, and Excretion. These stages illustrate how a substance is taken up, dispersed, chemically altered, and finally removed. Studying pharmacokinetics helps predict how a substance behaves and how long its effects last.
Melatonin Absorption and Distribution
When melatonin is taken orally, it is rapidly absorbed into the bloodstream, primarily from the gastrointestinal tract. Peak plasma concentrations are reached within 20 to 60 minutes after ingestion. However, a significant portion undergoes first-pass metabolism in the liver, reducing the amount that enters systemic circulation. This means only 3% to 33% of an oral dose becomes available, a measure called bioavailability.
Once absorbed, melatonin distributes widely throughout the body, readily crossing various biological barriers, including the blood-brain barrier. This allows melatonin to reach the brain and regulate sleep. Melatonin can also be found in other tissues and fluids, such as saliva, urine, and cerebrospinal fluid. Its widespread distribution allows it to interact with receptors in various organs, contributing to diverse physiological roles beyond sleep.
Melatonin Metabolism and Excretion
The body primarily breaks down melatonin in the liver, transforming the active hormone into inactive compounds. The main enzyme responsible for this initial breakdown is cytochrome P450 1A2 (CYP1A2), which converts melatonin into 6-hydroxymelatonin. This hydroxylation step is the rate-limiting part of melatonin’s metabolic pathway, dictating how quickly the hormone is processed. Other cytochrome P450 enzymes, such as CYP1A1 and CYP1B1, also play minor roles in this transformation.
Following the formation of 6-hydroxymelatonin, it undergoes further modification through conjugation reactions, primarily with sulfate or glucuronic acid. This process converts 6-hydroxymelatonin into more water-soluble forms, such as 6-hydroxymelatonin sulfate and 6-hydroxymelatonin glucuronide. These conjugated metabolites are efficiently cleared. The kidneys are the primary route of excretion for these metabolites, with about 80% eliminated in the urine. A small amount of unchanged melatonin is also excreted in the urine, but the majority is processed and eliminated as these inactive forms.
Factors Influencing Melatonin’s Journey
Several factors can alter how melatonin moves through and is processed by the body. Age plays a role, as older adults may experience reduced melatonin metabolism due to declines in liver function. This can lead to higher melatonin levels and a longer duration of action in elderly individuals. Organ health also matters; impaired liver or kidney function can lead to decreased metabolism and excretion, prolonging melatonin’s presence.
Drug interactions are another consideration, as certain medications can interfere with enzymes responsible for melatonin’s breakdown. Fluvoxamine, an antidepressant, inhibits the CYP1A2 enzyme, which can increase melatonin levels by slowing its metabolism. Caffeine can also inhibit CYP1A2, though to a lesser extent, potentially affecting melatonin concentrations. Conversely, some substances can induce CYP1A2 activity, leading to faster melatonin breakdown and potentially reduced effectiveness. The specific formulation also impacts its journey; immediate-release forms result in rapid peak levels and a shorter duration, while extended-release formulations provide a more sustained release and longer presence.