Naltrexone Half-life

Factors influencing how long Naltrexone will stay in your system

Half-life of Naltrexone

Naltrexone is a safe and effective medication that can help people struggling with Alcohol Use Disorder get their lives back on track.

In addition to knowing how it works to reduce dependency, knowing the half-life of naltrexone is important for a few reasons. First, it can help you to understand how long the medication will stay in your system. This is important for both medical and legal purposes.

Additionally, it can help you avoid the harmful effects of overdosing or underdosing, both of which can impact your efforts to reduce your drinking.

What is Naltrexone?

Naltrexone is a medication that is used to treat alcohol dependence and opioid dependence. It works by blocking the rewarding effects of alcohol and opioids in the brain, making it difficult to feel the desired effects of these substances. Usually taken as a tablet, it can also be injected or implanted.

By eliminating the “buzz”, it can gradually reduce your brain’s interest in drinking alcohol.

How does it work?

The first step to understanding the mechanism of action of naltrexone is to know how drug dependency sets in.

Drug dependency: The role of opioid receptors

Opioid receptors are a class of G protein-coupled receptors that are activated by endogenous opioid peptides as well as exogenous opioid drugs. These receptors are responsible for the analgesic (pain-relieving) effects of opioids. Opioid receptors are found in the brain, spinal cord, and gastrointestinal tract.

While there are four major types of opioid receptors:

  • mu
  • delta
  • kappa
  • nociceptin

Mu receptors are the relevant receptors in Naltrexone

After opioids stimulate these mu receptors, dopamine is released, giving rise to feelings of pleasure. While certain feedback mechanisms in the brain help overcome the urge to obtain pleasure in unsafe ways, this mechanism is compromised in people with addictions.

The stimulation of this reward system in the brain is the primary reason why people drink alcohol in the first place.

Antagonists: Blocking the Opioid Receptor

Receptor agonists and antagonists are two types of drugs that work by binding to receptors in the body. Agonists work by binding to and activating a receptor, while antagonists work by binding to a receptor and preventing activation.

Both agonists and antagonists can be used to treat various medical conditions. For example, agonists such as fentanyl and morphine can be used to treat pain, while antagonists such as spironolactone can be used to treat hypertension.


The film-coated tablets contain naltrexone hydrochloride. It is related to oxymorphone (an opioid analgesic) and naloxone (an opioid antagonist) but has a different structure.

Naltrexone hydrochloride tablets also have other ingredients including lactose monohydrate, crospovidone, colloidal anhydrous silica, magnesium stearate, hydroxypropyl methylcellulose, and polyethylene glycol.

Active metabolite

When taken orally naltrexone gets metabolized in the liver to 6 beta-naltrexol (the active metabolite) and other metabolites by dihydrodiol dehydrogenase enzymes.

A 50 mg standard dose of naltrexone hydrochloride exerts its opioid-blocking effect for 24 hours. Studies show that when the dose is doubled, the effects can last for 48 hours. The injectable form, given once a month, stays active for approximately four weeks.

Half-life of Naltrexone

Half-life is the time taken for the drug’s active metabolite levels to reduce by half. The half-life and peak levels of naltrexone depend on whether it is taken orally or administered as an injection.

When administered orally, about 96 percent of naltrexone is absorbed in the gastrointestinal tract. Within an hour, plasma levels of 6 beta-naltrexol and naltrexone peak.

A majority (53 percent to 79 percent) of 6 beta-naltrexol and naltrexone are excreted by the kidneys. Only a small amount (less than 2 percent of the dose) of unchanged naltrexone is excreted in the urine and the feces. Naltrexone is cleared through the kidneys, at a rate of 30 to 127 mL per minute whereas the clearance rate is between 230 and 369 mL per minute for 6 beta-naltrexol.

The elimination half-life value for 6-ß-naltrexol from orally administered naltrexone is 13 hours while the half-life of naltrexone is 4 hours.

When administered as an injection, the plasma concentration of naltrexone is achieved after 2 hours and a second peak occurs after two to three days. Plasma concentrations start to decline 14 days after the injection while the drug stays in the system for about a month.

The elimination half-life of naltrexone and 6 beta-naltrexol when the drug is administered as an injection is between 5 and 10 days.

While these are the estimated elimination values of naltrexone, the actual duration the medication stays in the system depends on multiple factors.

What factors affect the half-life of naltrexone?

The time it takes for naltrexone to leave your system can depend on a few things such as:

  • Age – It can take a longer time for older people to eliminate naltrexone from their system in comparison with younger people.
  • Metabolism – The elimination of naltrexone in people with a slower metabolism (such as those with thyroid conditions) may be slower compared to those with a faster metabolism.
  • Overall health – An individual’s overall health and the presence of any chronic illnesses influence the elimination of the drug.

Other factors that might play a role are hydration levels and the amount of body fat.

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Naltrexone is a semi-synthetic opioid with competitive antagonist activity at mu opioid receptors. Its efficacy has been demonstrated in the treatment of alcohol and opioid dependence, but adherence to daily dosing has been recognized as a factor limiting long-term effectiveness. Recently, a long-acting injectable formulation of naltrexone has received FDA-approval for treating alcohol and opioid dependence. This article reviews the pharmacology of naltrexone, the current evidence supporting the use of extended-release naltrexone, and the clinical challenges in the induction of patients to this medication.

Keywords: Addiction; Alcohol dependence; Naltrexone; Opioid dependence; Toxicology.