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How Long Does Subutex Stay In Your System?

Subutex is a drug that was approved by the FDA in 2002 for the treatment of opioid dependence.  It is typically utilized as an agent in opioid replacement therapy to help individuals transition off of more potent (often illicit) opioidergic drugs such as oxycodone and heroin.  In other words, an individual who was previously ingesting a drug like heroin could successfully use Subutex to aid in the discontinuation process.

The active ingredient within Subutex is “buprenorphine” which functions principally as a mu-opioid receptor (MOR) partial agonist, but also modulates function of kappa and delta receptors (to a lesser extent).  Partial agonism of the mu-receptor delivers potent opioidergic stimulation, but not quite to the same extent as drugs like heroin.  As a result, it is able to attenuate most discontinuation effects of potent opioids, thereby allowing addicts to successfully function in society.

Despite the appeal of taking Subutex to treat opioid dependence, many people realize that the buprenorphine component can be an addictive drug in itself.  For this reason, many addicts have decided to kick all opioids – including those taken for opioid replacement therapy in attempt to attain sobriety.  After quitting, however, many individuals wonder how long Subutex stays in their system.

How long does Subutex stay in your system after stopping?

If you’ve stopped taking this drug, you can expect to experience substantial Subutex withdrawal symptoms, many of which may be severe.  During the process of discontinuation, many users contemplate how long Subutex will remain in systemic circulation after their final dose.  To determine how long Subutex stays in your system after cessation, it is necessary to consider the half-life of its active ingredient, buprenorphine.

Buprenorphine has an elimination half-life of approximately 37 hours when administered sublingually.  Since Subutex is solely manufactured in the form of sublingual tablets, we can conclude that it’ll take around 37 hours to eliminate 50% of buprenorphine from circulation.  Based on the 37 hour half-life, we can estimate that buprenorphine will stay in your system for 8.5 days (on average).

Other research suggests that the elimination half-life may be longer at nearly 42 hours, which would mean clearance could take an average of 9.6 days.  Although buprenorphine may be cleared from your system in under 10 days, it doesn’t mean that all components of Subutex have been excreted.  Buprenorphine is broken down in the liver by various enzymes to form the metabolite “norbuprenorphine.”

The norbuprenorphine metabolite has a longer elimination half-life than buprenorphine, meaning it stays in your body for a longer period after discontinuation.  The half-life of norbuprenorphine is documented at 57 hours.  This indicates that metabolites of Subutex could remain in your system for over 13 days after quitting.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/buprenorphine
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8889672
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9684393

Variables that influence how long Subutex stays in your system

Despite the fact that the time it takes to clear Subutex’s active ingredient “buprenorphine” from circulation is around 8.5 days, not everyone clears it at this speed.  Similarly, not everyone excretes the metabolite norbuprenorphine in the average time of 13 days.  Some people may fully excrete Subutex and metabolites in under 2 weeks, while others may take considerably longer than 2 weeks.  Variance in excretion time is usually subject to individual variation based on variables such as: the individual, term of administration, dosage, and co-ingestion of other drugs.

  1. Individual factors

If two people take the same dose of Subutex (8 mg) for the same duration, and cease usage the same day, why could one individual excrete the drug quicker than the other?  Differences in excretion speed are largely a result of complex individual factors.  Examples of such factors that influence elimination half-life of buprenorphine (and norbuprenorphine) include: age, body mass, genetics, liver function, and urinary pH.

Age: Many reports indicate that elderly individuals (those over 65 years of age) often have difficulty metabolizing drugs.  It is possible that the buprenorphine within Subutex may undergo significantly slower metabolism in an elderly individual compared to a younger healthy adult (or adolescent).  Elderly individuals tend to have reduced hepatic blood flow, which may increase buprenorphine’s elimination half-life.

Other factors that may prolong systemic clearance of buprenorphine among elderly include: age-related health conditions, other pharmaceutical medications, and/or reduced physiologic capacity.  Though not scientifically validated, it should be hypothesized that elderly patients may retain buprenorphine and norbuprenorphine for a longer duration after their final Subutex dose.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21124750

Body mass + Fat (%): It may be necessary to consider your body mass when considering how quickly you’re likely to excrete Subutex.  Some speculate that the higher your body mass (height/weight), relative to the dosage of Subutex you ingest – the quicker you’re likely to excrete the drug.  In other words, if you’re tall and hefty, you may excrete an 8 mg dose faster than someone who’s short and petite.

Furthermore, it is thought that individuals with a high percentage of body fat may exhibit increased elimination half-lives of buprenorphine and norbuprenorphine metabolites.  This presumption stems from the fact that buprenorphine is highly lipophilic and binds to fat stores.  Individuals with greater body fat may accumulate more of the drug within their fat, thus extending the clearance period.

  • Source: http://www.ncbi.nlm.nih.gov/books/NBK64152/

Genetics: The buprenorphine hydrochloride within Subutex is metabolized principally by CYP3A4 isoenzymes in the liver.  There is some evidence to suggest that individuals may metabolize buprenorphine at rapid, extensive (normative), or poor rates based on their CYP3A4 genes.  There’s an entire spectrum of metabolizers ranging from: ultrarapid metabolizers to poor metabolizers.

A small percentage of the population are considered “poor metabolizers” in that their CYP3A4 function is significantly reduced.  As a result of this poor metabolism, levels of buprenorphine accumulate and half-life is extended.  On the other hand, a rapid metabolizer may efficiently process buprenorphine as a result of optimal CYP3A4 function – thereby expediting clearance.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15966752

Hydration: To a small extent, the degree to which a person is hydrated could affect clearance speed and excretion of Subutex post-ingestion.  A person who is suboptimally hydrated (or dehydrated) could be thought to excrete buprenorphine (and its metabolites) at a slower rate than individuals who stay hydrated.  This is likely a result of urinary flow rate as influenced by a person’s hydration.

When you stay well-hydrated, you’re able to maintain a heightened urinary flow rate compared to someone that’s dehydrated.  This increased urinary flow rate is thought to result in faster, more efficient excretion of drugs like buprenorphine as well as its metabolites.

Liver function: Enzymes in your liver are responsible for metabolizing buprenorphine within Subutex.  If your liver function is compromised such as via a condition like cirrhosis, you won’t be able to efficiently metabolize buprenorphine.  As a result, the drug will accumulate to a greater level throughout your body and elimination half-life will increase.

Hepatic impairment usually decreases CYP3A4 isoenzyme function, as well as other CYP450 isoenzymes that may contribute to the metabolism of buprenorphine.  If you have compromised liver function, you probably shouldn’t expect to excrete Subutex as quickly as someone with a healthy liver.  The more severe your hepatic impairment, the longer you can expect to retain the drug prior to excretion.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12799931/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15966752

Metabolic rate: A person’s BMR (basal metabolic rate) can influence drug metabolism and clearance speed.  Individuals with higher BMRs are thought to burn more energy at rest, and as a result, are able to excrete buprenorphine faster than usual.  Those with lower BMRs burn less energy at rest, and are thought to excrete buprenorphine at a slower rate.

The influence of metabolic rate on metabolism, clearance speed, and excretion may not be significant, but it may play a subtle role.  If you consider yourself to have a high BMR, your final dose of Subutex may get cleared quickly compared to a person with a low BMR.

Urinary pH: People with acidic urine tend to excrete drugs faster and with greater efficiency than those with alkaline urine.  If you’re eating foods that are considered “basic” or “alkaline,” you may retain buprenorphine and norbuprenorphine metabolites for much longer than usual in your urine.  If you eat a diet comprised mainly of acidic foods, the clearance rate of buprenorphine may increase, leading to a reduced elimination half-life (especially compared to individuals eating alkaline foods).

  1. Term of Administration (Acute vs. Chronic)

How long you’ve been taking Subutex can certainly have an effect on the duration it stays in your system after your final dose.  Buprenorphine hydrochloride, the active ingredient, is highly lipophilic, meaning it extensively binds to bodily tissues and fats.  When administered acutely (on a short-term basis), buprenorphine is unlikely to accumulate to the extent that it would if administered chronically (over a long-term).

Short-term users are unlikely to have accumulated peak levels of the buprenorphine and metabolites within tissues, and further, are less likely to be taking high doses.  Since acute administration is associated with lower doses, the drug is more efficiently metabolized, and less norbuprenorphine metabolites are formed – resulting in quicker clearance.

Chronic or long-term users are likely to have accumulated peak levels of buprenorphine and norbuprenorphine throughout their bodily tissues.  Additionally, since long-term users are likely to be taking high doses (as a result of tolerance), the metabolism is likely to be less efficient and more norbuprenorphine metabolites are likely to form.  When considering the accumulation and dosages of long-term users – systemic excretion is likely to take longer.

  1. Dosage (4 mg to 24 mg)

Subutex is manufactured in 2 mg and 8 mg sublingual tablets.  Medical sources indicate that most users take anywhere from 4 mg to 24 mg per day.  It is understood that the greater the dosage a person takes (especially relative to their bodyweight), the longer they are likely to retain the drug in their system before elimination.

At high dosages such as 24 mg per day, a greater total quantity of buprenorphine is ingested.  At this level, the liver must work harder to metabolize such a high dose, which could prolong the metabolism process.  Consequently, a greater number of norbuprenorphine metabolites will be formed in the liver as a result of this substantial dose.

This will result in a greater amount of buprenorphine and norbuprenorphine circulating throughout the body, leading to increased tissue accumulation compared to smaller doses.  At low dosages of just 4 mg, liver enzymes metabolize the drug with greater efficiency, less metabolites are formed, and reduced accumulation occurs within tissues.  Therefore, if you’re taking a high dose (especially over a long-term), it may take longer to clear from your body than someone taking a low dose.

  1. Co-ingestion of drugs (CYP3A4)

If you’re taking another drug (or supplement) along with Subutex, it could affect your ability to break down buprenorphine hydrochloride.  Drugs or supplements that specifically affect function of CYP3A4 isoenzymes tend to have the greatest influence on buprenorphine’s half-life.  Some of these drugs may “inhibit” or interfere with CYP3A4 function; these are classified as CYP3A4 inhibitors.

CYP3A4 inhibitors essentially prevent optimal metabolism of buprenorphine.  In other words, someone taking a CYP3A4 inhibitor could facilitate “intermediate” metabolism as opposed to “extensive” metabolism – and “poor” metabolism instead of “intermediate” metabolism.  Examples of drugs that are likely to increase half-life of Subutex as a result of their inhibitory effects on CYP3A4 include: Clarithromycin, Chloramphenicol, Indinavir, Ketoconazole, and Ritonavir.

Other drugs facilitate “induction” or increased function of CYP3A4; these are classified as CYP3A4 inducers.  Someone taking a CYP3A4 inducer is likely to metabolize buprenorphine quicker than usual, resulting in faster excretion. Examples of known CYP3A4 inducers include: Carbamazepine, Modafinil, Oxcarbazepine, Phenobarbital, Rifampicin, and St. John’s wort.

Subutex (Buprenorphine HCl): Absorption, Metabolism, Excretion

Following sublingual administration of Subutex, the pharmacologically active ingredient “buprenorphine” is rapidly absorbed through mucous membranes within the mouth.  The absorption is not influenced by the duration over which the tablet remains under the tongue.  Despite its rapid absorption via oral mucosa, its absorption throughout the rest of a the system is significantly slower.

It undergoes extensive first-pass metabolism within the liver, principally by CYP3A4 isoenzymes.  Specifically, CYP3A4 isoenzymes facilitate N-dealkylation of buprenorphine to form the primary metabolite norbuprenorphine; CYP2C8 also plays a minor role.  As a result of first-pass metabolism, buprenorphine has a low bioavailability of just 31% and takes between 40 minutes and 3.5 hours to reach peak concentrations within the bloodstream.

An estimated 96% of buprenorphine binds to plasma proteins (alpha and beta-globulin), and as a result of its high lipophilicity, it is distributed widely throughout the body.  Buprenorphine is thought to accumulate within bloodstream and tissues with chronic dosing until it reaches a steady state concentration.  The elimination half-life of buprenorphine within Subutex is estimated at 37 hours, meaning it takes nearly 8.5 days to clear it from your system.

The norbuprenorphine metabolite has an elimination half-life of approximately 57 hours, meaning it takes longer to clear from your system than buprenorphine.  It may take nearly 2 weeks (14 days) for an individual to have completely excreted norbuprenorphine metabolites.  Prior to excretion, both buprenorphine and norbuprenorphine are subject to glucuronidation, forming glucuronides.

Glucuronidation of buprenorphine is elicited by UGT1A1 and UGT2B7 microsomes to form “buprenorphine-3-glucuronide” (B3G), whereas glucuronidation of norbuprenorphine is elicited by UGT1A1 and UGT1A3 to form “norbuprenorphine-3-glucuronide” (N3G).  Most of these glucuronides are excreted from the body through feces and bile, whereas 10% to 30% are excreted via urine.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/buprenorphine
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15966752

Types of Subutex Drug Tests

There are various types of drug tests that may be utilized to assess for the presence of buprenorphine and its primary metabolite norbuprenorphine.  Though buprenorphine is not tested for on a standard SAMHSA-5 test, it could be detected on a more advanced drug screening.  Ways to test for buprenorphine within a person’s system include: urine tests, hair tests, saliva tests, and blood tests.

Urine tests: If you’ve been taking Subutex, you won’t need to worry about testing positive for opioids on a SAMHSA-5 screening.  The only detectable opioids on a standard urinary drug test are those that metabolize into morphine; buprenorphine is not one of these.  However, if you are subject to a more extensive urinalysis, buprenorphine will likely be detectable.

The cutoff level for buprenorphine on a urinary test is typically set at 5 ng/mL, meaning if you have over 5 ng/mL in your system, you’ll test “positive.”  Those that have been taking buprenorphine are likely to have over 160 ng/ml in their system.  In urine testing, fresh urine samples are typically analyzed via liquid chromatography/mass spectrometry (LC/MS) for increased accuracy.

Urine tests are often preferred over saliva and/or blood tests because they are minimally invasive, yet provide a longer window of detection.  The buprenorphine may become detectable within just 40 minutes of Subutex administration, and remain in the urine for nearly 2 weeks (in the form of norbuprenorphine metabolites) following your final dose.  Generally, chronic (long-term) users of Subutex will likely have more buprenorphine (and norbuprenorphine) within their urine than acute (short-term) users.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/14607001
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25663675

Blood tests: It is possible to detect buprenorphine via collection of a blood sample.  That said, blood tests are typically inconvenient due to the fact that they’re highly invasive and provide a shorter window of detection than a urine screening.  Following administration of Subutex, the buprenorphine content may become detectable within minutes, and remain detectable for over a week thereafter.

It’s easiest to detect buprenorphine approximately 40 minutes to 3.5 hours after Subutex administration because this is when levels peak in the bloodstream.  That said, the drug will be present in lesser amounts prior to peaking, as well as following its peak.  Furthermore, trace amounts of the drug could appear within the bloodstream for weeks after discontinuation among chronic users.

Among chronic users, buprenorphine (and norbuprenorphine) accumulate in tissues throughout the body.  As the person detoxifies by abstaining from Subutex, the accumulated buprenorphine is gradually released from tissues and makes its way into the bloodstream prior to systemic clearance.  For this reason, a long-term (or chronic) user is more likely to test positive for buprenorphine on a blood test than a short-term (or acute) user.

Techniques such as high-performance liquid chromatography/mass spectrometry (HPLC/MS) can be used to pinpoint even tiny amounts of buprenorphine (and norbuprenorphine) within the bloodstream.  Norbuprenorphine is likely to show up for a longer duration, hence testing for this metabolite may be preferred over its parent buprenorphine.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15240036

Hair tests: Buprenorphine will accumulate within outgrowths of hair follicles on an individual’s head and/or other parts of their body.  One drawback associated with hair testing for buprenorphine is that there’s a time gap between when a person takes the drug, and when it appears within their hair.  It often takes several days or weeks following ingestion of buprenorphine for it to appear in outgrowths of hair.

However, one major advantage of hair testing is that the buprenorphine often remains detectable for a much longer duration compared to other forms of testing.  It is speculated that buprenorphine (and norbuprenorphine) may remain detectable for several months after ingestion within a person’s hair, possibly longer in a chronic user.  Research suggests that among users of Subutex, entire hair follicles contain an average of 105.2 pg/mg buprenorphine and 156.8 pg/mg norbuprenorphine.

The length and color of a person’s hair may influence detectability of buprenorphine in hair outgrowths.  That said, proximal segments (most recent outgrowths) tend to contain the greatest amount of buprenorphine and metabolites.  Only a minimal amount of hair is required to detect buprenorphine at a threshold of 10 pg/mg.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24817054
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24713865
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21301858

Saliva tests: Another way to detect ingestion of a buprenorphine-containing drug is via an oral fluid sample.  A saliva test involves collecting an oral fluid sample and sending it to a laboratory for analysis.  Saliva tests may be preferred over blood tests due to the fact that they aren’t as invasive and levels of buprenorphine within saliva are generally similar to those found within a person’s bloodstream.

As a result, saliva tests are capable of detecting buprenorphine (and norbuprenorphine) for up to a week after administration, perhaps longer in a chronic user.  Furthermore, the buprenorphine may be detectable within saliva sooner than within the blood due to the fact that it is administered sublingually. If a person recently administered the drug (under their tongue), there may still be traces (or remnants) of undiffused buprenorphine within their oral fluid – resulting in rapid detection.

It is thought that in future years salivary testing will be preferred over blood testing because it will be equally as accurate and less invasive.  New technology is emerging that aims to analyze a saliva sample within just minutes to determine whether drugs are present within a person’s system, and their precise levels.  Law enforcement agents may use saliva samples to determine whether an individual is experiencing buprenorphine intoxication.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21219701

Who could get tested for Subutex? (Buprenorphine HCl)

Although testing for buprenorphine (the active ingredient within Subutex) is considered relatively uncommon compared to other opioids, it is still possible to test for.  A variety of individuals ranging from criminals to rehabilitation patients may be mandated to participate in buprenorphine drug testing.

  • Athletes: Collegiate and professional athletes are unlikely to use Subutex as a performance enhancer.  For this reason, the active ingredient buprenorphine is seldom assessed for on athletic drug tests. Only in rare cases could an athlete suspected of abusing opioids be tested for a chemical like buprenorphine.
  • Criminals: A criminal may be tested for buprenorphine, especially if a law enforcement agent suspects that the criminal is intoxicated on an opioidergic substance.  Should a criminal get caught with unauthorized buprenorphine in his/her system, a harsh penalty may be the consequence.
  • Employees: Many employers require employees to maintain vigilance, alertness, and attention to detail.  Vigilance and wakefulness are especially important for truck drivers, machinists, and those operating heavy machinery.  Since Subutex can cause drowsiness, an extensive drug panel that tests for buprenorphine may be required prior to employment and/or to maintain a current job.
  • Military: Members of the military are known for staying sober and maintaining peak levels of arousal.  One slip up as a result of drowsiness or lack of attention could result in a fatal mistake.  For this reason, tests for drugs like buprenorphine which can decrease arousal may be administered to troops.
  • Rehab patients: Someone in rehabilitation for drug abuse may be tested regularly to determine whether they’ve maintained sobriety.  Extensive drug tests capable of detecting buprenorphine may be administered at random among rehab patients.  Should the individual get caught with buprenorphine in his/her system – they may necessitate a longer stay at the rehab facility.

How to get Subutex out of your system

There are several tricks that may be effective for expediting the excretion of Subutex (and its metabolites).  Understand that prior to consideration or implementation of these tricks, you should always verify their safety with a medical professional.  Additionally, realize that not everyone will derive benefit from the ideas listed below.

  1. Quit taking it: It’s common sense that the sooner you stop taking Subutex, the quicker it’ll be eliminated from your system. In reality, the best way to ensure that the drug is out of your body is to cease usage for an extended duration. The longer you’ve been off of Subutex, the less likely it is to remain lingering within your bodily tissues.
  2. Burn fat: It’s known that buprenorphine is lipophilic and capable of accumulating in fat stores throughout the body, especially when administered chronically at high doses. To detoxify your body of Subutex as quickly as possible, burning fat can help. The greater the amount of fat you burn, the faster you’ll have excreted the drug from your system.  Fat burning is often best accomplished via strategic diet and exercise.
  3. CYP3A4 induction: Taking any substance that ramps up CYP3A4 isoenzymes will result in more efficient metabolism of buprenorphine and possibly its metabolites. Quicker metabolism may promote faster excretion, leading to rapid systemic clearance. Understand that certain substances may be more potent CYP3A4 inducers than others.  Professional consultation is recommended before using enzymatic inducers.
  4. Activated charcoal: Taking activated charcoal may help rid your body of Subutex quicker than usual. Activated charcoal is capable of binding to endotoxins within your gut, as well as any remnants of buprenorphine and norbuprenorphine circulating throughout your system. For this reason, I recommend activated charcoal as being among the best supplements for drug withdrawal.  That said, always discuss safety of activated charcoal supplementation with your doctor.
  • Source: http://www.ncbi.nlm.nih.gov/books/NBK64152/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11153617

How long has Subutex stayed in your system after stopping?

If you’ve taken Subutex (Buprenorphine Hydrochloride), share a comment below regarding how long you believe it stayed in your system after your final dose.  To help others understand your situation, note some specifics such as: the dosage of Subutex you were taking, how long you took it, and whether you took other medications (especially those that affect CYP3A4).  Do you believe you excreted the buprenorphine faster or slower than average?

Understand that most people will have eliminated buprenorphine from their systems within 10 days of stopping, and the norbuprenorphine metabolites should be cleared within 2 weeks.  If you have any tricks that you used to expedite the excretion of buprenorphine, discuss them in the comments section.

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