What is Suboxone? What is Suboxone used for?
Suboxone is a Brand name for a medicine that contains fixed combination of buprenorphine and naloxone. Active ingredients buprenorphine and naloxone are together in strategic 4:1 ratio. Buprenorphine is an opioid/narcotic medication while Naloxone blocks the effects of opioid medication, including pain relief euphoria during opioid abuse. This combination is used to treat dependence on heroin or other opioids. Suboxone comes as a sublingual tablet or a film tablet you put in your cheek or under your tongue. Suboxone is manufactured by Reckitt Benckiser pharmaceuticals. It is available on the market since 2002 and has high popularity as a result of its efficacy and low abuse potential compared to other opioid replacement agents such as methadone.
How does Suboxone works in the body?
Buprenorphine, the active substance of Suboxone is a derivative of the opioid alkaloid drug called thebaine that is a 25-40 more potent and longer lasting analgesic than morphine. It seems to work as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of agonist activity on delta opioid receptors has been proposed to account for the observation that buprenorphine tolerance may not develop with chronic use. The binding to the mu and kappa opioid receptors produces hyperpolarization and reduced neuronal excitability. Additionally, buprenorphine has a very slow dissociation from its receptor. Its receptor fixation half-life is about 40 minutes which is certainly longer than morphine that counts in milliseconds
Naloxone is the other active substance of Suboxone. This drug works as an opioid receptor antagonist and has no agonist activity. It is a competitive antagonist of mu, delta, and kappa opioid receptors. Studies showed that naloxone has the strongest binding at mu opioid receptors
The mixture of these opioidergic effects can make a neurophysiological “high” characterized by: elevated mood, pleasure, physical relaxation, reduced anxiety, and CNS depression.
How Long Does Suboxone Stay In Your System?
If patients abruptly stop taking this drug, they may experience substantial Suboxone withdrawal symptoms. In order to define how long the drug stays in your system after taking last dose, it is necessary to consider elimination half-life time of Suboxon, concretely the elimination half-lives of its most dominant active ingredients buprenorphine, but also naloxone. The buprenorphine elimination half-life time is calculated to be 37 hours, and this is considered as extremely long time.
Body needs about 2 full days to excrete the half of buprenorphine dose after Suboxone administration. Considering the 37 hour buprenorphine’s elimination half-life, it could be calculated that this drug can be fully cleared from your system in less than 9 days. In comparison with buprenorphine, Naloxones elimination half-life time is between 30 minutes and 1 hour 20 minutes. This means that the naloxone is cleared from the body much before buprenorphine. Most patients will eliminate naloxone after 8 hours of administration as a result of its short half-life time. It is important to mention that even though the elimination half-life of buprenorphine is about 37 hours, it is degraded into metabolite called “norbuprenorphine” which has even longer half-life time that exceeds 37 hours. Hence the specific elimination half-life of the metabolite “norbuprenorphine” hasn’t been well studied and confirmed for exaxct calculation, it is likely that Suboxone will remain in the body for longer than 9 days meaning that its metabolites may remain into your system for theoretically up to 2 weeks after last dose is taken. Thus buprenorphine’s half-life time is far more important to consider when Suboxone elimination is in question.
Factors that may influence how long Suboxone stays in system?
Alhough the regular time for Suboxone clearance from the system is about 9 days, some people may need longer time to excrete the drug, while others eliminate the drug faster. Factors that may influence the elimination speed differences may include: individual factors (age, weight, liver/renal function, genetics, metabolic rate, hydration urinary pH), frequency of use, dosage and co-administration of other drugs.
How age may influence Suboxone elimination?
Even though there aren’t any specific studies that have analyzed differences in absorption, distribution, and metabolism of Suboxone in the elderly who are 65+ or older, it doesn’t mean there are no differences. Many health professionals consider that elderly patients are more likely to eliminate Suboxone at a substantially slower rate than younger adults. The extended elimination half-life of Suboxone in elderly patients may be caused by reduced hepatic blood flow, health problems, polymedication, and/or decreased overall physiologic functionality.
How body weight and height (body mass) may influence Suboxone elimination?
Your height or weight correlated with Suboxone dose you take may influence elimination of this drug. Usually the greater Suboxone dose is taken and the lower is the body mass, the longer will stay in your system. The lower the dosage of Suboxone is taken, and the greater is body mass, the shorter it will stay in your body after administration.
How percentage of body fats may influence Suboxone elimination?
Since Suboxone is combination of lipophilic substances, it will accumulate well within lipid tissues, and fats throughout the body. The greater is a person’s percentage of body fat, the longer they are likely to accumulate Suboxone predominantly the buprenorphine. Patients with a low percentage of body fat may clear Suboxone much faster than patients with high body fat.
How genetics may influence Suboxone elimination?
Genetics is also individual factor that may influence the pace Suboxone is metabolized. Genes that regulates process of CYP3A4 enzyme activation within the liver could an impact whether buprenorphine is efficiently or poorly metabolized. Those who are known as fast metabolizes may excrete buprenorphine faster than a poor CYP3A4 metabolizer. Although CYP3A4 may not have a significant impact on elimination half-life time of Suboxone, it may have an indirect one.
How metabolic rate may influence Suboxone elimination?
Basal metabolic rate or BMR may have an influence on how rapid are drugs eliminated from the body. Since the buprenorphine is lipophilic compound, it will accumulate within body tissues and fat stores. Those with faster metabolic rates usually have less body fat because of the fact that they’re burning more energy at rest and as a result, they eliminate buprenorphine in less time. However, those with a slow basal metabolic rate will burn fewer energy at time of rest, and may have a larger amount of buprenorphine stored in fat.
How hydration may influence Suboxone elimination?
The level to which person stays hydrated may influence the elimination rate of Suboxone. Those who stay well hydrated often show greater urinary flow rates in comparison to those who are dehydrated, which may result in quicker systemic clearance. The elimination time of Suboxone in well-hydrated persons may be considerably less than that of a dehydrated person.
How urinary pH may influence Suboxone elimination?
Urinary pH may also influence how long Suboxone stays in their system. Patients with acidic urine will predominately eliminate Suboxone more rapidly than patients who have alkaline urine. Highly alkalinized urine may prolong the elimination half-life time by several hours, although acidified urine may do the opposite and decrease the half-life by hours.
How the liver function may influence Suboxone elimination?
Patients suffering from liver diseases such as cirrhosis may have prolonged half-life of Suboxone. The liver is responsible for Suboxone metabolism, and if it is functionality compromised, less of Suboxone will be metabolized. Lower metabolism rate will leads to a greater amount of the drug accumulating in the body.
Since patients with liver disease may have decreased expression of CYP3A4 enzymes elimination of Suboxone will be prolonged. In general, the more severe the impairment is, the longer is the elimination time.
How the dosage may influence Suboxone elimination?
The administration dose of Suboxone may affect how long it stays in the body before it is fully eliminated. The greater the dosage of Suboxone is, and if you frequently administered it, the longer it will stay in your system after discontinuation. On the other hand, the lower the dose of Suboxone is, the shorter is the duration of staying in the system after stopping. Patients taking buprenorphine 2mg/ naloxone 0.5mg are considered to be taking a “low dose” combination and thus should eliminate the drug from their system more efficiently. Patients taking buprenorphine 12mg/ naloxone 3 mg combination are considered to be taking a “high dose” and may clear the drug with reduced efficiency consequently extending the elimination time. The higher dosages also have a greater overload on hepatic enzymes, causing in less efficient metabolism, which may prolong elimination. So, liver can’t metabolize high doses of buprenorphine as well as lower doses because there is a larger amount of buprenorphine to metabolize. A lower dose doesn’t have an impact on the liver to the same degree as a high dose, therefore is metabolized more efficiently, resulting in faster elimination.
How the frequency of use may influence Suboxone elimination?
When considering how long Suboxone stays in your body after discontinuation, it is necessary to consider how frequently it is used as well as the total time length over which is used. The more frequent Suboxone is used it is more likely to remain longer time in your system after discontinuation. Frequent users are patients who uses sublingual tablets once or twice per day, whereas an infrequent user may take them as needed.
Suboxone sublingual tablets should be taken once daily. Though, patient compliance is not always adequate, resulting in some patients taking Suboxone more or less frequently than once per day. Those who use Suboxone sublingual tablets more than once per day will most likely end up accumulating more drug and its metabolites and resulting in slower excretion compared to daily users.
Additionally, frequent Suboxome users often become tolerant to low doses and end up taking high doses thus prolonging the excretion. Those who are taking Suboxone “as needed” will likely not accumulate important amounts of the drug in the body and perhaps will not have built up a tolerance to lower doses. As a result, irregular users tend to clear the drug much faster from their systems when stopping. Also, the duration in which patient has taken Suboxone regularly can also have an impact on elimination half-life time. Those who are using Suboxone at least once per day during a period longer than 1 week will likely have longer clearance periods than paitents who took the drug for less than a week and/or infrequently. This is because of the fact that long-term users will have accumulated peak levels of buprenorphine within their body tissue, and are much more likely to be taking high doses as a result of cumulative tolerance.
How the coadministration of other drugs may influence Suboxone elimination?
Coadministration of other drugs orsubstance may enhance your body’s ability to metabolize Suboxone. Metabolism alteration may serve to either: faster or prolonged elimination of Suboxone. Since the buprenorphine within Suboxone is metabolized mainly by CYP3A4 isoenzymes in the liver, drugs that significantly affect expression of these enzymes will affect its clearance.
Drugs that work as CYP3A4 inhibitors may prolong elimination of buprenorphine. Some of the most potent CYP3A4 inhibitors are: Clarithromycin, Indinavir, Ketoconazole, Chloramphenicol, Nefazodone, and Ritonavir. Those who take some of these drugs together with Suboxone, may have Suboxone elimination half-life to be longer than usual.
Other drugs or substances known as inducers of CYP3A4 are known to enhance expression of CYP3A4 isoenzymes, therefore metabolizing buprenorphine and naloxone faster. Potent CYP3A4 inducers may include: Carbamazepine, Modafinil, Glucocorticoids, Oxcarbazepine, Phenobarbital, Rifampicin, and St. John’s wort. If you have taken any of these drugs together with Suboxone, its elimination half-life may be shorter than expected.
How long does Suboxone stay in blood, urine, saliva, hair?
The maximum concentrations of buprenorphine in bloodstream will be in approximately 2 hours after ingestion, making it easily detectable on the day of administration. After some days the detectability of buprenorphine will drop. It has been showed that buprenorphine and its metabolite “norbuprenorphine” could be detectable in a blood sample for days possibly weeks after last dose is taken.
It can be expected from Suboxone to become detectable in urine within 40 minutes of administration and remain present in urine for weeks. If high doses are taken frequently during long-term it is possible to be test positive after 2 weeks of administration. One study described that the total buprenorphine amount administered over a 12 month period was associated with the amount present in urine samples.
Nevertheless it may take days or even weeks after initial administration to detect Suboxone in the hair; it is supposed that this drug will remain detectable for an extremely long duration 1 to 3 months after post-ingestion.
Theoretically, Suboxone will remain detectable within a saliva sample for days, possibly weeks after ingestion.