Ambien (Zolpidem) is a popular medication prescribed for the treatment of insomnia. It is classified as a “nonbenzodiazepine” due to the fact that it shares a similar mechanism of action with benzodiazepines, but differs in its chemical structure. Ambien delivers its sedative, hypnotic (sleep-inducing) effects by modulating receptors of GABA (gamma-amino-butyric-acid).
It specifically functions primarily as a full agonist at the GABA(A) receptor (alpha 1 subunit) to induce sleep. Following administration of the standard version of Ambien, users tend to fall asleep within 15 minutes. Since the standard version of Ambien is solely helpful for falling asleep, but not staying asleep – many individuals with insomnia prefer the controlled-release (CR) version to maintain their slumber.
Despite the growing popularity in sleeping pill usage, many users are realizing that adverse effects and possible deleterious long-term effects fail to justify Ambien’s use. Examples of such adverse effects include: memory impairment (linked to dementia), impaired motor skills (increasing likelihood of car accidents), nausea, dizziness, and hallucinations. For these reasons, many Ambien users have stopped taking the drug and want to clear it from their system.
How long does Ambien stay in your system? (Zolpidem Half-Life)
Assuming you’ve taken your last dose of this drug, and possibly experienced Ambien withdrawal symptoms, you’re probably wondering how long it stays in your system. The active ingredient within Ambien known as “Zolpidem” has a half-life ranging between 2 to 3 hours; some sources estimate approximately 2.6 hours in healthy adults. This means that after you’ve ingested your last dose, your body will have excreted 50% of it within just several hours.
However, for complete 100% excretion of zolpidem, it’ll take slightly longer. Based on the estimated 2 to 3 hour half-life, full systemic clearance is likely to take anywhere from 11 hours to 16.5 hours. On average, most people should clear it from their system within around 14 hours after ingestion.
Despite complete clearance of zolpidem in under 33 hours, it is unclear as to whether various metabolites such as: zolpidem phenyl-4-carboxylic acid (ZPCA) zolpidem 6-carboxylic acid (ZCA) linger for a slightly longer duration. Most research suggests that these metabolites are likely to be cleared from the urine within 3 days.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/zolpidem
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17555642
Variables that influence how long Ambien stays in your system
Although we understand that Ambien has an extremely short half-life of 2 to 3 hours, and complete systemic elimination takes (on average) around 14 hours, not everyone will clear the drug in an “average” speed. Some people will excrete the zolpidem from their systems rapidly, quicker than 14 hours, while others may excrete the zolpidem at a slower rate (longer than 14 hours). Variables that affect clearance times include things like: individual attributes, dosage ingested, frequency/duration of usage, and co-administration of other drugs.
Two people may take the same dosage of immediate-release Ambien for the same duration, yet one person may excrete the drug quicker and more efficiently than the other individual. This is generally due to a variety of individualized attributes including: a person’s age, body mass, genetic variation, hepatic function, and urinary pH. Understand that certain individual attributes will either expedite clearance of zolpidem or prolong it.
Age: It is widely understood that most drugs, including Ambien are excreted slower among elderly (age 65+) individuals compared to younger adults and adolescents. This prolonged clearance among the elderly is thought to be primarily a result of lower concentrations of free testosterone. Other factors that may affect clearance in elderly include: decreased hepatic blood flow, reduced physiologic efficiency, other health conditions, as well as ingesting other medications – in elderly patients.
Research has shown that clearance rates are slower and half-life of the drug increases by approximately 1.2 hours in elderly individuals, suggesting that it could take nearly 25 hours for systemic clearance of zolpidem. Younger men with high testosterone tend to metabolize and excrete the drug much more quickly than elderly users. As a result of its prolonged clearance time among those aged 65+, Ambien is typically prescribed at lower doses in elderly users.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12919178
Body mass: It is thought that a person’s body mass (relative to the dosage of Ambien they’re taking) can affect systemic clearance. Usually the greater the dose of zolpidem a person ingests relative to their body mass, the longer it will stay in their system. If a tall/large individual takes a 5 mg dose of Ambien, it is thought that he/she would excrete it sooner than a short/small person.
This is due to the fact that a larger body size can generally handle greater doses and process them more efficiently than a smaller one. Though body mass may not play a significant role in excretion time, it is important to realize that it likely affects clearance speed (even if to a nearly negligible extent). Additionally, since Ambien is water soluble and body fat contains little water, it may get excreted quicker in individuals with a greater percentage of body fat.
Genetics: Research has shown that certain genes that influence expression of hepatic enzymes that can affect the metabolism of Ambien. Specifically, individuals with the CYP3A4*18 allele exhibit enhanced expression of CYP3A4 isoenzymes. CYP3A4 isoenzymes are chiefly responsible for metabolizing zolpidem. Enhanced expression of CYP3A4 as a result of the CYP3A4*18 variant results in faster metabolism and possibly quicker clearance.
On the other hand, individuals with the CYP2C19*2 allele exhibit markedly poorer metabolism of zolpidem. This is due to the fact that CYP2C19*2 reduces expression of CYP2C19 isoenzymes which play a role in zolpidem’s metabolism. Should you have either the CYP3A4*18 or the CYP2C19*2 allele, you may excrete zolpidem faster or slower than average.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22964165
Food intake / Hydration: It is evident that eating prior to ingestion of any drug could potentially affect its absorption. Individuals that ate a big meal prior to taking Ambien may absorb the drug at a slightly slower rate compared to those taking it on an empty stomach. The slight difference in absorption speed may inevitably have a slight influence on clearance time.
In addition to whether you ate food prior to taking your final dose of Ambien, hydration is thought to affect clearance speed. The more hydrated an individual is when they take Ambien, the greater their urinary flow rate is likely to be. Increased urinary flow rate is associated with faster systemic clearance of drugs. Therefore staying hydrated could clear the zolpidem faster from a person’s system via urination compared to remaining dehydrated.
Liver function: Those with hepatic impairment may experience a slower clearance of zolpidem from their system compared to individuals with normative liver function. This is due to the fact that zolpidem is metabolized by various CYP450 isoenzymes in the liver. When a person’s liver isn’t working properly, the ability to metabolize zolpidem via these enzymes becomes compromised.
Evidence suggests that the elimination half-life of zolpidem among patients with hepatic cirrhosis is extended to ~9.9 hours; substantially longer than healthy adults. This means that it could take up to 5 days for complete excretion of zolpidem (and its metabolites). If you have poor liver function, it may take [significantly] longer for your body to metabolize and excrete zolpidem.
Metabolic rate: A person’s basal metabolic rate (BMR) indicates how much energy they burn at rest and often affects metabolism and clearance of various drugs. Individuals with high BMRs are burning more energy at rest, and thus may metabolize and excrete Ambien faster than those with lower BMRs. If you have a high BMR, you’ll metabolize zolpidem quicker, whereas if you have a low BMR, you’ll metabolize it slower – possibly taking longer to clear it from your system.
Sex: Another important factor that influences clearance speed of zolpidem from your system is your “sex.” Men tend to metabolize and excrete the drug substantially quicker than women primarily due to testosterone levels. Levels of plasma testosterone of at least 2.88 mcg/mL are associated with optimal expression of CYP3A4 isoenzymes, leading to efficient metabolic breakdown of zolpidem.
Since women are unable to generate 2.88 mcg/mL of plasma testosterone, the expression of CYP3A4 is blunted. This not only leads to 50% greater peak serum concentrations of zolpidem following ingestion, but a prolonged clearance period. For this reason, it should be suspected that women may be at the slower end of the zolpidem clearance spectrum (16.5 hours) compared to the faster end of 11 hours.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20552178
Urinary pH: It is understood that the more acidic a person’s urinary pH, the quicker they’ll excrete zolpidem. This is due to the fact that an acidic urinary pH prevents reabsorption of zolpidem metabolites (ZPCA and ZCA) prior to excretion. Individuals with a high urinary pH or “alkaline” urine may experience significantly slower clearance speed of zolpidem by comparison.
It is thought that the half-life of zolpidem among those with highly alkalinized urine may be potentially hours longer than individuals with acidic urine. Since dietary intake largely affects your urinary pH, the foods you’ve been eating will likely alter clearance speed of zolpidem. People that typically eat a lot of meats are likely to have acidic urine, whereas those who eat lemons, limes, dates, figs, carrots, etc. – are likely to have more alkaline urine.
- Source: http://www.nhtsa.gov/people/injury/research/job185drugs/zolpidem.htm
Dosage (5 mg to 10 mg)
The greater the dosage of Ambien you took prior to discontinuation, the longer it may take to excrete from your body. This is primarily due to the fact that larger doses of zolpidem take longer to metabolize via liver enzymes and ultimately excrete. Excretion times can be extended among higher dose users because once the drug has been fully metabolized, more is circulating throughout a person’s body.
As a result of a greater amount of zolpidem circulating throughout the body, it doesn’t get excreted as efficiently. Since there’s more metabolites formed with larger doses, a greater amount may be susceptible to reabsorption prior to elimination in a high dose user. On the other hand, taking smaller doses of the drug (e.g. less than 5 mg) should facilitate the quickest possible elimination.
Lower doses are easier to metabolize within the liver, and levels of metabolites are lower from the start, resulting in less total time for complete systemic clearance. Understand that dosage can have a significant impact on clearance, especially when analyzed relative to a person’s body mass, liver function, and testosterone levels.
Co-ingestion of drugs
Assuming you take other medications (or even supplements), it is necessary to understand that they could affect Ambien’s metabolism and clearance speed. Since Ambien is chiefly metabolized by CYP3A4 isoenzymes in the liver, any drugs that serve to either upregulate or downregulate CYP3A4 functionality could affect clearance rate. Drugs known as CYP3A4 “inhibitors interfere with CYP3A4 enzymes, whereas CYP3A4 “inducers” enhance their expression.
Common examples of CYP3A4 inhibitors include: Clarithromycin, Indinavir, Ketoconazole, Nelfinavir, Ritonavir, and Saquinavir. Should you be taking any of these inhibitory agents (or one not mentioned), the functionality of your CYP3A4 enzymes will be compromised. This will impair your ability to metabolize Ambien, leading to an extended clearance period.
Notable examples of CYP3A4 inducers include: Butalbital, Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin, Rifampicin, and St. John’s wort. If you’re taking an agent that induces activity of CYP3A4 enzymes, the ingested Ambien will be metabolized quicker than usual. This expedited metabolism is thought to reduce its half-life and facilitate faster excretion.
- Source: http://www.nhtsa.gov/people/injury/research/job185drugs/zolpidem.htm
Frequency of Administration
The more frequently a person takes Ambien, the more likely it will remain in their body for a longer duration. Though the active ingredient “zolpidem” is highly hydrophilic, meaning it is unlikely to bind to fat stores, frequent administration could still result in greater accumulation of zolpidem metabolites prior to excretion. As a result of greater accumulation of zolpidem metabolites it will take longer to fully detoxify or clearance of zolpidem from the body.
Most medical sources suggest that Ambien is meant to be administered once per day prior to sleep, however, not everyone always follows these instructions. Certain individuals may administer the drug more frequently than what is medically advised, thereby taxing their liver to metabolize multiple doses of the drug, which inevitably produces greater levels of metabolites. The more metabolites circulating throughout your system, the longer they will likely take to excrete.
In addition to frequency of ingestion, it may be necessary to consider duration over which an individual has taken Ambien. Someone who took the drug just one day will not accumulate zolpidem metabolites to the extent as an individual who’s consistently been taking it for weeks, months, or years. Consistent long-term usage is associated with higher dosages (as a result of tolerance), metabolite accumulation (as a result of the extended term of administration), and ultimately prolonged clearance.
Ambien (Zolpidem): Absorption, Metabolism, Excretion (Details)
Following oral administration of Ambien, the active ingredient “zolpidem” is quickly absorbed by the gastrointestinal (GI) tract. Though the hypnotic effect elicited by zolpidem is experienced by users within 15 minutes, peak plasma concentrations are attained within 30 minutes to 3 hours post-ingestion. Zolpidem is considered hydrophilic, meaning it is highly soluble within bodily water (fluid) and has an average distribution volume of 0.54 L/kg in healthy adults.
Approximately 35% of an ingested dose is subject to first-pass metabolism in the liver, where it is metabolized by various CYP450 (cytochrome P450) enzymes. During first pass metabolism of zolpidem, an estimated: 61% is broken down by CYP3A4 enzymes, 22% by CYP2C9 enzymes, 14% by CYP1A2 enzymes, and less than 3% by CYP2D6 and CYP2C19 enzymes. Metabolites formed in the process include: zolpidem phenyl-4-carboxylic acid (ZPCA) zolpidem 6-carboxylic acid (ZCA).
All of the metabolites formed from zolpidem are considered pharmacologically inactive. The elimination half-life of zolpidem is approximately 2.6 hours, indicating it gets excreted from the body quickly (along with its metabolites). It takes approximately 13.5 hours to fully clear zolpidem metabolites from your system.
Elimination of these metabolites is facilitated primarily via the kidneys. Up to 56% of zolpidem metabolites (mostly ZPCA) is excreted within the urine. An estimated 37% of zolpidem metabolites are excreted through feces.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/zolpidem
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014868/
Types of Ambien Drug Tests (Zolpidem Detection)
Many individuals are concerned about whether Ambien (Zolpidem) could show up on a drug test. Most standardized drug tests such as the SAMHSA-5 will not be capable of detecting zolpidem. However, more extensive tests are capable of detecting the presence of zolpidem metabolites. Various types of drug tests that can be used to detect Ambien include: urine tests, blood tests, hair tests, and saliva tests.
Urine tests: Due to the fact that unchanged zolpidem only accounts for 1% of the drug when excreted via urine, most urine tests assess for the presence of metabolites. The most prominent metabolite of zolpidem is known as “ZPCA” (zolpidem phenyl-4-carboxylic acid). A urine sample is capable of determining whether someone has ingested Ambien for up to 72 hours (3 days) following their last dose.
Since ZPCA accounts for 51% of an Ambien dose excreted via urine, detection levels are set at approximately 2 ng/mL. Urine is typically analyzed with gas chromatography/mass spectrometry (GC/MS) to confirm exact levels of ZPCA metabolites. Because urine testing is convenient, non-invasive, and provides accurate results – it is the preferred way to test for Ambien usage.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17555642
Blood tests: Following ingestion of 5 mg Ambien, peak concentrations in the blood are attained within ~1.6 hours. The specific concentrations of zolpidem are usually a result of the dosage ingested. Peak levels of a 5 mg dose are 0.06 mg/L whereas peak concentrations from a 10 mg dose are double at around 0.20 mg/L. In general, the higher the dosage a person takes, the easier it is to detect Ambien on a blood test.
Though blood testing is seldom preferred over urine testing due to the fact that it is invasive, it can be used by medical professionals to detect a potential overdose. Furthermore, blood tests to detect zolpidem may be utilized among hospital patients and/or intoxicated drivers. Though the drug becomes detectable in the bloodstream in less than 30 minutes, it doesn’t remain detectable for as long as a urine test.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22673707
Hair tests: A hair test can be utilized to detect the presence of zolpidem long after ingestion. It is estimated that hair can be collected 3 to 5 weeks after suspected ingestion of zolpidem and accurately determine whether the drug was administered. Hair analyses typically involve collecting a sample of hair follicles (from the head) at least 3 cm in length.
These samples are then analyzed in “picograms per milligram” to determine zolpidem accumulation. Just one dose of zolpidem can yield hair concentrations ranging from 1.8 pg/mg to 9.8 pg/mg; the concentration can depend on the dose. Though hair testing is accurate, it must be conducted weeks after the suspected “ingestion.” For this reason, hair testing is generally reserved for criminal cases.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15240037
Saliva tests: It is possible to detect zolpidem in a person’s saliva within just 15 minutes of oral administration. Research suggests that zolpidem remains detectable in oral fluid for up to 8 hours after ingestion. Though the window of detection is relatively short in oral fluid samples, saliva tests are often preferred over other modalities for the sake of convenience; they are non-invasive and easy to collect.
In addition, new technologies are emerging that will allow law enforcement agents to collect a saliva sample (as opposed to a urine or blood sample) and instantaneously determine whether the individual has a drug in his/her system. In fact, these technological detectors are becoming so advanced, that in future years they may be able to instantly detect zolpidem in an oral fluid sample with a high degree of accuracy.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15458723
Who could get tested for Ambien?
There are a variety of individuals that theoretically “could” get tested for Ambien. Since Ambien isn’t considered a major substance of abuse, it is rarely assessed for on standard drug tests (e.g. SAMHSA-5). Certain individuals such as: criminals, employees, and rehab patients may be subject to advanced drug testing that is capable of detecting Ambien.
- Criminals: Ambien is becoming a popular “date rape” drug due to its fast-acting hypnotic effect. For this reason, if a law enforcement agent suspects that a criminal may have administered Ambien to a victim, that victim will be tested. In addition, criminals in general may be tested for Ambien due to the fact that it is sometimes abused.
- Employees: Some employers will test their employees for the presence of nonbenzodiazepine sleeping pills like Ambien. Any jobs requiring employees to operate heavy machinery (e.g. construction) and/or motor vehicles (e.g. truck drivers) need to minimize likelihood of mistakes. An employee operating with Ambien in his/her system may not only be unproductive, but could make a potentially deadly mistake. For this reason, if an employee is caught with zolpidem in his/her system, that individual may be fired.
- Military troops: Those in the military need to be able to think quickly, follow orders, and be highly aware of their environment. A person in the military with Ambien in his/her system may compromise the safety of other troops such as while operating machinery, weaponry, or driving a motor vehicle. Should Ambien get detected in the urine of someone in the military, that person may be delisted and/or relegated from duties.
- Rehab patients: Individuals in drug rehabilitation facilities may be tempted to use (or abuse) Ambien. For this reason, they may be subject to extensive drug tests that are capable of detecting prescription drugs like zolpidem. If a rehab patient is caught with zolpidem in his/her system (on an unauthorized basis), they may face penalization or necessitate a longer stay at the rehab facility.
Tips to clear Ambien from your system
Though it won’t take long to clear Ambien from your system, you may want to know of ways in which the clearance process can be expedited. Below is a list of tips that could be used to speed up clearance of zolpidem and its metabolites. Always confirm safety of these tips with a medical professional prior to implementation.
- Fully discontinue: This tip isn’t rocket science, but something that most people don’t understand. If you want to completely rid your body of zolpidem and its metabolites, you’ll need to stop taking it for several days. If you continue to use it on a daily basis, you’ll never fully excrete the drug.
- Acidify urinary pH: Evidence suggests that urinary pH can alter clearance of various drugs, including that of Ambien. If you want to ensure that the drug is cleared as quickly as possible from your body, you’ll want to maintain an acidic urine. This means eating foods such as: meats, grains, chocolate, etc. to reduce your urinary pH.
- Maintain hydration: Some people think that by drinking a ton of water, they’ll be able to clear Ambien quicker than normal. Staying optimally hydrated is thought to hasten the excretion of zolpidem (and metabolites) because it increases urinary flow rate. However, it is never recommended to go “overboard” as toxicity can result from drinking too much water.
- CYP3A4 induction: Taking a supplement (or drug) that acts as a CYP3A4 inducer could speed up metabolism and clearance of Ambien. Obviously you should never take anything without authorized medical recommendation for the sole purpose of clearing zolpidem from your system. That said, if you happen to get medical permission to take a CYP3A4 inducer and verify safety (e.g. contraindications), your clearance rate could be quicker than usual.
How long has Ambien stayed in your system?
If you’ve stopped taking Ambien, share a comment mentioning how long you believe it has stayed in your system following your final dose. Do you think you’re excreting the drug (and its metabolites) faster than normal or at a slower rate? Provide reason as to why you may have excreted Ambien at a slower or faster rate than usual such as: hepatic impairment, testosterone levels, co-administration of other drugs, etc.
To help others get a better understanding of your situation, share individual factors that may affect clearance speed of Ambien such as: your age, dosage you were taking, and how long you had been taking it. Realize that for the majority of users, Ambien (and its metabolites) are unlikely to stay in your system for more than 1 day after your final dose. However, there will be slight variation in clearance (e.g. +/- a few days) based on the individual.