How Long Does Phenobarbital Stay In Your System And Its Mechanism Of Action

Last Updated: November 12, 2021

Authored by Roger Weiss, MD

Reviewed by Michael Espelin APRN

Phenobarbital is a DEA Schedule IV controlled substance under the barbiturates drug class. It is mainly used for the management of seizures, but it’s antipsychotic and brain-slowing properties also make it suitable for anxiety relief. Phenobarbital may also be prescribed to patients who suffer from addiction to another barbiturate drug, and are to stop taking them, with its purpose to prevent withdrawal symptoms.

Phenobarbital mechanism of action centers around the gamma-aminobutyric acid A (GABA-A) receptor, a neurotransmitter with central nervous system (CNS) inhibitory activity. While the drug’s onset of action takes quite longer than other barbiturates, there is very little difference when it comes to the duration of Phenobarbital and other barbiturates’ effects. More information about this, the half-life of the drug, and the Phenobarbital MOA will be discussed in this article. Of course, the most common questions are How long does Phenobarbital stay in your system and How does Phenobarbital work? will be addressed.

Phenobarbital Mechanism Of Action

Phenobarbital mechanism of action is central to the function of the medication – all of what Phenobarbital does comes down to how it acts on the body. While the Phenobarbital mechanism of action has not been fully explained and clarified, what is known is that the Phenobarbital MOA begins with the medication binding to GABA-A receptors and activating them, increasing synaptic inhibition and neuronal responsivity to GABA.

It Also Inhibits the Calcium Uptake Into Neurons and Acts as an Antagonist on the Following:

  • Neuronal acetylcholine receptor subunit alpha-4
  • Neuronal acetylcholine receptor subunit alpha-7
  • Glutamate receptor 2
  • Glutamate receptor ionotropic, kainate 2
  • NMDA receptor

In simpler words, Phenobarb reduces the frequency of seizures and the likelihood of them occurring. This medication also has sedative-hypnotic and anticonvulsant effects, which are believed to be related to its GABA-A activity-enhancing abilities. That said, Phenobarb is not used solely for the treatment of seizures – it may also be used for the treatment of several other conditions such as anxiety, insomnia, and status epilepticus, among others. This drug was also proven to be helpful in managing withdrawal symptoms stemming from the use of benzodiazepines, alcohol, and other barbiturates.

A medical worker holds Phenobarbital pill in her hand.

Phenobarbital Metabolism And Excretion

Phenobarb is metabolized hepatically, mostly via the CYP2C19 enzyme. When taken orally, 70 to 90% of the drug is slowly absorbed from the gastrointestinal tract, and 90% of it is absorbed within 2 hours. When it comes to the rate of absorption or metabolism of this drug, there are several influencing factors, with the biggest one being the route of administration. Generally, Phenobarb’s onset of action ranges from 20 to 60 minutes following oral or rectal administration, and within 1 to 5 minutes following IV administration. The kind of diet a person has may also affect the drug’s metabolism. For instance, someone on a low protein diet may process it faster since lower protein binding may increase its distribution from plasma to tissues.

Hydroxylation of this drug produces an inactive metabolite called p-hydroxyphenobarbital, which is then excreted as glucuronic acid conjugates. This metabolite makes up about 75% of what is excreted in the urine, whereas the remaining 25% is excreted as unchanged Phenobarbital. In a study involving rats that were injected with Phenobarb, it was found that urine elimination peaks after around 7 hours (on average) following administration.

How Long Does It Take For Phenobarbital To Work?

When taken orally, Phenobarbital’s peak concentrations in the blood and the brain are reached within 8 to 12 hours and 10 to 15 hours, respectively. Its sedative effects usually last for 6 to 8 hours following oral administration. On the other hand, when administered subcutaneously, sedative effects usually last for only 3 to 6 hours. This route of administration, however, has a relatively fast onset of action that occurs within 5 minutes. The therapeutic effects of the drug are also achieved faster – within only 30 minutes. While it is much more fast-acting when administered subcutaneously, the duration of action is not as long, being only 4 to 6 hours.

How Long Does Phenobarbital Stay In Your System?

The duration that Phenobarb or Luminal stays in one’s system usually depends on several factors including the half-life of Phenobarbital, the age of the user, their metabolism levels, and the way it was administered. These factors affect how long the drug stays in one’s system differently and depending on a person’s biological makeup, so the length of time Phenobarbital stays in the system will vary from person to person.

How Long Does Phenobarb Stay In Blood

Blood tests are the most accurate method of testing for barbiturates since they check for parent compounds of a drug rather than its metabolites. It is estimated that a Luminal blood test may detect it in the system for up to a week after taking a prescribed dose. It may last longer if the dose is higher and taken for recreational purposes.

How Long Does Phenobarb Stay In Urine

This is perhaps the most popular method of drug testing, especially in an employment setting. When it comes to Phenobarb, the liver puts the substance through a metabolization process once it is entered into one’s system, and the toxic remainder is removed from the body through urine. Due to this process, it can appear in a urine test for a considerable period. Phenobarbital is detectable from the first urine collected at 2 hours up to 15 days after taking the drug.

How Long Does Phenobarb Stay In Saliva

This method is mostly used for quick and recent drug detection. It also measures the parent compound of the drug. A higher concentration generally means that a high amount of the substance is present in one’s system. Phenobarbital is detectable in saliva or oral fluid within 15-60 minutes of administration, and it stays in readily detectable concentrations for up to 2 days in the saliva.

How Long Does Phenobarb Stay In Hair

A hair test is conducted to determine the drug use of a person over a long period. A strand of hair is tested for traces of the drug, and it is useful mostly for illicit drugs and for people who have been substance users for a long time. For Phenobarbital, hair tests can detect it for up to 90 days after taking the last dose.

Half-Life Of Phenobarbital

The half-life of Phenobarbital is on the longer side, which allows for once-a-day dosing (if tolerated by the patient) for the treatment and management of seizures. In adults, the half-life of Phenobarbital ranges from 53 to 118 hours, with a mean of 79 hours. In newborns and children, on the other hand, the half-life of Phenobarbital is longer, ranging from 60 to 180 hours with a mean of 110 hours. Once it is introduced to one’s system, physicians conduct blood test procedures to determine the right dose that effectively keeps the medicine in its therapeutic range. While the average Phenobarb half-life is around 79 hours, individual factors affect the elimination time of this drug from the system. And so, elimination will vary from patient to patient.

Factors Affecting Phenobarbital Detection Window

There are many factors affecting the length of time barbiturates like Phenobarbital remain detectable in the body. These factors may include one’s body mass, overall health, the dose they are taking, and the frequency of administration.

Generally, patients with a higher body mass have a slower metabolism, which then results in a longer detection window because their system eliminates the drug slower than usual. Old age also means slower metabolism due to poor overall health, so the detection window will be longer as well. And of course, higher dosage and more frequent use would lengthen Phenobarbital’s detection window.

Phenobarbital drug test results paper.

Phenobarbital On a Standard Pre-employment Drug Test

Most employers have a drug-free workplace program in place, and the kind of test given will vary from workplace to workplace. Testing for Phenobarbital, for instance, would depend on the kind of screening one has to take for a particular employment. 5-panel and 10-panel tests are the most common tests used in workplace drug-testing programs to detect the presence of alcohol and other substances in one’s system.

A standard 5-panel test is the most commonly used test in workplace drug screening. This test looks for the presence of marijuana, cocaine, phencyclidine (PCP), amphetamines, and opiates. A 5-panel does not test for barbiturates, and so, it won’t detect the presence of Phenobarb in a job candidate’s system.

10-panel tests, on the other hand, are a more thorough screening covering an additional five drugs. Apart from the ones included in the five-panel test, this test also checks for barbiturates, benzodiazepines, methadone, methaq, ualone, and propoxyphene. That said, it can tell if a job candidate uses barbiturates, the drug class Phenobarbital falls under.

Removing Phenobarbital From The System Safely

While there is no foolproof way of entirely removing Phenobarb from one’s system fast, there are several things one can do to accelerate the body’s natural removal process of drugs, especially when they are experiencing Phenobarb toxicity because of overdose, or discomforting adverse reactions to the drug.

Following are the three main things that a person who has had a Luminal dose can do to ensure that they are supporting the body’s natural removal process.

  • Drinking plenty of water– Consuming water as much as possible keeps the body well hydrated and helps the physical bodily functions to happen with ease. With this method, one is “flushing” out the drugs from the body since urine is one of the most efficient and effective ways that the body gets rid of toxins. It usually takes several days for this method to be fully efficient. Over a few days, drinking plenty of water will ensure that the concentration of drugs in the system will be diluted.
  • Following a nutritious diet with additional vitamins– Getting rid of a potent drug from the system requires the body to do extra work in the process of metabolizing the substance and removing the toxins. This is why it is essential to avoid saturated fats and sugars and make sure the diet consists of food that is easy to digest and nutritious. Continuing an unhealthy diet is likely to prolong the natural removal process of the drugs.
  • Exercising– This method is called “sweating out” the drugs. As one sweats and burns fat through vigorous exercise, it helps remove any Phenobarb metabolites and remaining residue of the drug from the body through sweat.

Note that these tips will not be helpful in case of drug dependence, as Phenobarb long-term use can cause withdrawal. Contact the medical professional and get addiction treatment together with support and care. Specialized rehab centers provide a safe and compassionate environment while assisting in the recovery.

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Page Sources

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Published on: July 3rd, 2019

Updated on: November 12th, 2021

About Author

Roger Weiss, MD

Dr. Roger Weiss is a practicing mental health specialist at the hospital. Dr. Weiss combines his clinical practice and medical writing career since 2009. Apart from these activities, Dr. Weiss also delivers lectures for youth, former addicts, and everyone interested in topics such as substance abuse and treatment.

Medically Reviewed by

Michael Espelin APRN

8 years of nursing experience in wide variety of behavioral and addition settings that include adult inpatient and outpatient mental health services with substance use disorders, and geriatric long-term care and hospice care.  He has a particular interest in psychopharmacology, nutritional psychiatry, and alternative treatment options involving particular vitamins, dietary supplements, and administering auricular acupuncture.