Prednisone is a common synthetic corticosteroid medication that was initially synthesized in 1955. Upon ingestion of prednisone, it doesn’t elicit significant biological effects until converted via the liver to the pharmacologically active chemical “prednisolone.” Prednisolone functions as an irreversible glucorticoid receptor agonist, binding to alpha glucorticoid receptors (AlphaGRs) and beta glucorticoid receptors (BetaGRs) within bodily tissues to reduce inflammation.
In addition to being an anti-inflammatory agent, prednisone is an effective immunosuppressant drug, exerting effects by modifying gene transcription, reducing activity within the lymphatic system (e.g. T-lymphocytes), decreasing levels of immunoglobulin, and minimizing travel of immune complexes through basement membranes. As a result of prenisolone’s widespread physiological effects (some of which aren’t fully understood), the drug can be used to effectively treat a variety of medical conditions including: asthma, COPD, CIPD, ulcerative colitis, Chron’s disease, multiple sclerosis, and more.
Though prednisone is an extremely helpful medication when no other treatments are available, it is akin to using a pill-based atomic bomb; it may effectively hit the target (treat the medical condition), but there are often other casualties (severe adverse effects) incurred throughout the process. For this reason, prednisone is often reserved as a “last resort” or emergency treatment for serious medical conditions. Since treatment-induced adverse effects can linger well-after a person has discontinued treatment, many wonder whether prednisone is still in their system after stopping and for how long.
How long does Prednisone stay in your system after stopping?
If you’ve stopped taking this drug, you may end up facing some pretty serious Prednisone withdrawal symptoms. As these symptoms emerge, you may feel infuriated and confused – wondering when the drug will have been eliminated from your body, and when you’ll feel normal again. To determine how long Prednisone stays in your system after stopping, it is important to consider its half-life.
The half-life for all formats of Prednisone (immediate-release and delayed-release) ranges from 2 to 3 hours after conversion to “prednisolone.” This means that in approximately 3 hours, 50% of the dose you ingested will have been cleared from systemic circulation. If considering the 2 to 3 hour documented half-life, the Prednisone should theoretically be cleared from your system between 11 and 16.5 hours post-ingestion.
Some sources suggest that the half-life of pharmacologically active “prednisolone” may be slightly longer than 2 to 3 hours. One source suggests that its half-life could be 2 to 4 hours with an average of ~3.6 hours. This would indicate that elimination of prednisolone concentrations from systemic circulation would take just under 20 hours.
In other words, both Prednisone and prednisolone should be cleared from your body within a 24 hour period after stopping. However, just because you no longer have prednisone circulating throughout your bloodstream certainly doesn’t mean you should be feeling 100% better. Prednisolone facilitates numerous physiological alterations throughout your body that could linger for a long-term following discontinuation.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/prednisone
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/prednisolone
Variables that influence how long Prednisone stays in your system
On average, it takes up to 17 hours to eliminate Prednisone from systemic circulation, and up to 20 hours to clear prednisolone, not everyone fits the “average” clearance duration. Some people are thought to clear the drug significantly faster than 17 to 20 hours, whereas others may be unable to clear it for over 24 hours after their last dose. Variables such as: individual attributes, Prednisone dosage, term of administration, and co-ingestion of other drugs – account for differences in clearance speed.
Two people could begin taking prednisone at the exact same time, with the same dose and format, and cease usage in sync – yet one person may clear the drug quicker than the other individual. The differences in clearance speed are often chalked up to individual factors such as: a person’s age, body mass, genetics, liver/kidney function, and urinary pH. For example, someone with renal/hepatic impairment may retain the drug for significantly longer than a person in good health.
Age: There may be differences in clearance times of prednisone (and prednisolone) among young adults compared to elderly. Elderly individuals (age 65+) often exhibit reduced hepatic blood flow, lower albumin levels, poorer overall physiologic function, and are more likely to be taking medications that could interfere with clearance of Prednisone. For this reason, the elimination time of Prednisone could be prolonged among those over 65.
Some research suggests that young children may also exhibit differences in clearance speed of prednisolone compared to adolescents and adults. The half-life of prednisolone is thought to be an average of 3.6 hours in children, which is longer than most adults. The elimination half-life of prednisolone (and prednisone) among healthy adults is 2 to 3 hours.
Body mass: Generally, the greater a person’s body mass relative to the dose of prednisone they ingest, the quicker they’re able to excrete it. More massive individuals can usually handle a slightly greater amount of an exogenous substance compared to smaller people. For this reason, if the same dose of prednisone were administered to a tall/heavy person as a short/light person – it would likely be excreted in the former faster than the latter.
Genetics: Since Prednisone is converted by 11-beta-hydroxysteroid-dehydrogenase to form prednisolone, specific genes aren’t thought to have a major influence on its metabolism. However, prednisolone is metabolized by CYP3A4 enzymes within the liver. CYP3A4 enzymes are thought to be influenced by various genes, resulting in rapid or poor metabolism of the drug.
Individuals with specific CYP3A4 alleles may metabolize prednisolone faster than those with different alleles. As a result of expedited metabolism, the drug may get cleared quicker from systemic circulation. On the other hand, poor metabolizers of prednisolone may take substantially longer to clear it from their system.
Food intake: Though medical documentation suggests taking Prednisone with food to avoid gastrointestinal distress, there is evidence that absorption of prednisolone may be affected. One study noted that taking enteric-coated prednisolone tablets along with food could delay absorption by nearly 12 hours, resulting in prolonged drug retention following ingestion. Though other research suggests that prednisone doesn’t significantly alter absorption times, it should be considered that food could have a slight effect on systemic clearance.
If food does in fact delay Prednisone absorption by several hours, the drug will be metabolized at a later time than had a person taken it on an empty stomach. This means that Prednisone remains in a person’s body for a longer total duration. Assuming you ate a large meal with your final dose of Prednisone, realize that it may not be excreted as quickly as had you taken it in a fasted state.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/2598978
Liver / Kidney function: There is some evidence to suggest that among individuals with hepatic impairment, the elimination half-life of Prednisone is extended. Not only does hepatic impairment interfere with the conversion of Prednisone to prednisolone, but it interferes with the metabolism of prednisolone.
The half-life of Prednisolone is noted as being as being as high as 10.3 hours among those with hepatic abnormalities. This means that complete systemic clearance could take 2.36 days. Additionally, renal impairment are known to excrete prednisone (and its metabolites) at a slower rate than those with normative kidney function.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22777155
- Source: http://www.ncbi.nlm.nih.gov/pubmed/4639403
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3909980
Metabolic rate: A person’s BMR (basal metabolic rate) is known to affect drug clearance. BMR is influenced by a variety of factors such as genetics, exercise habits, dietary intake, and sleep. Individuals with high BMRs tend to metabolize and excrete drugs quicker than those with lower BMRs.
If you consider yourself to have a “fast metabolism,” you may excrete prednisone near the quicker end of the clearance spectrum (i.e. 11 hours). Whereas if you consider yourself to have a “slow metabolism,” prednisone may linger in your system for a longer period (i.e. 16.5 hours). Realize that metabolic rate may not have a significant effect on excretion time, but it could facilitate differences in clearance times potentially by minutes (or hours).
Oral contraceptives: Women taking oral contraceptives may interfere with the enzymatic metabolism of both Prednisone and prednisolone in the liver. Oral contraceptives typically contain an estrogenic component, affecting hepatic enzyme activation and plasma proteins. Co-ingestion of an oral contraceptive along with Prednisone increases peak serum concentrations and its elimination half-life.
The ingestion of oral contraceptives results in poorer non-renal clearance of prednisolone and reduced binding of prednisolone to albumin and transcortin. As a result prednisolone clearance decreases by 30%. If you take contraceptives along with prednisone, it could linger in your system for up to 22 hours after your final dose.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6734709
Urinary pH: Prednisone is metabolized in the liver, processed by the kidneys, and excreted in the urine as free and conjugated metabolites. It is known that a person’s urinary pH (alkaline vs. acidic) can impact the speed by which drugs are cleared from the body. Individuals with alkaline urine (high pH) tend to excrete substances like Prednisone less efficiently than those with acidic urine (low pH); acidification of urine prevents reabsorption prior to excretion, whereas alkaline urine allows it.
Dosage (1 mg to 80 mg)
The greater the dosage of Prednisone someone takes, the longer it will stay in their system. This is due to the fact that administration of high doses means there’s a greater amount of the drug to metabolize, and ultimately a greater number of metabolites formed in the process. As a result, someone taking Prednisone at a dosage of 80 mg per day will metabolize and excrete it at a slower rate than someone taking just 10 mg per day.
Furthermore, the lower dose user taking 10 mg will only have 5 mg in systemic circulation after 2-3 hours, whereas the individual who took 80 mg will have 40 mg remaining in circulation after 2-3 hours. In addition, a greater amount of prednisolone metabolites will be formed in the system of a person taking a higher dose. Research has shown that changes in the elimination half-life of the prednisolone metabolite are dose-dependent.
In other words, the greater the dose of Prednisone you’re taking, the longer you can expect the metabolite “prednisolone” to linger in your system. Certain individuals believe that the drug could accumulate in a person’s body with higher doses as well. Though accumulation isn’t scientifically supported, accumulation of high doses can occur among those with hepatic and/or renal impairment.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7310640
Term of administration
The longer the duration over which a person has been taking Prednisone, the more likely they’ve accumulated peak levels of prednisolone throughout their system. Successive, frequent administration of Prednisone will eventually lead to a “steady state” concentration. Someone that’s been medicated with Prednisone daily for a long-term will have reached a peak, steady concentration of the drug throughout their body.
On the other hand, someone that’s been taking Prednisone for a just one day will not have reached a steady state, peak concentration of the drug. For this reason, it is thought that clearance time in an extremely short-term user will be considerably less than that of a long-term Prednisone user. Additionally, long-term users generally take higher doses of the drug (because they’ve built up a tolerance), which is known to prolong elimination.
Taking other drugs
Simultaneously taking other drugs (or supplements) along with Prednisone could affect its metabolism and excretion. Though Prednisone itself isn’t significantly affected by ingestion of other drugs, the metabolite prednisolone could be excreted at a much slower pace. Drugs that affect CYP3A4 isoenzymes in the liver are thought to have the greatest impact on prednisolone clearance.
Substances that “inhibit” or interfere with CYP3A4 function are known to prolong the elimination of prednisolone. Examples of such inhibitors of CYP3A4 function include: Ritonavir, Indinavir, Nelfinavir, Clarithromycin, Telithromycin, Ketoconazole, etc. Should a person ingest any of these agents along with Prednisone, they may significantly increase the elimination half-life of prednisolone – thus taking longer to clear from your system.
Other substances that “induce” or enhance CYP3A4 function are thought to expedite clearance of prednisolone. Examples of CYP3A4 inducers include: Carbamazepine, Phenytoin, Phenobarbital, Rifampicin, Rifabutin, Modafinil, and more. Should you be taking any of these substances along with Prednisone, the half-life of prednisolone may be reduced.
Prednisone: Absorption, Metabolism, Excretion (Details)
Following oral administration of Prednisone, it is efficiently absorbed by the gastrointestinal (GI) tract. It then undergoes first pass metabolism in the liver and is converted into the pharmacologically active metabolite “prednisolone.” Metabolism of Prednisone to form prednisolone occurs via the enzyme 11-Beta hydrozysteroid dehydrogenase (hydrogenation of the ketone group at position 11).
Prior to its conversion to prednsiolone, Prednisone has a half-life of just 1 hour. However, post-conversion to prednisolone, its half-life is extended between 2 to 4 hours. Research has shown that ingestion of a 50 mg tablet yields peak serum concentrations reach an average of 930 mcg/L. Prednisone binds to plasma proteins such as albumin and serum concentrations peak within 1-2 hours post-administration.
Peak concentrations are followed by an exponential decrease in serum levels after 2 hours. Hepatic enzymes facilitate additional breakdown of prednisolone to form metabolites such as: prednisone (11-oxo metabolite), 6-Beta-OH-prednisolone, 20-Beta-OH-prednisolone, 20-Alpha-OH-prednisolone, 20-Alpha-OH-prednisone, 20-Beta-OH-prednisone, and various tetrahydro epimers of each. A total of 10 metabolites have been identified from prednisolone metabolism.
Prior to excretion, metabolites undergo glucuronidation or are coupled with sulfate via 3-hydroxyl. The drug is excreted via urine as free and conjugated metabolites along with unchanged prednisolone. The half-life of Prednisone is 2 to 4 hours, meaning a majority of the drug and its metabolites will have been excreted within 24 hours after your final dose.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/prednisone
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/prednisolone
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3543199
Note: There is a slight difference in peak maximum serum concentration in delayed-release Prednisone formats. Delayed-release formats are estimated to reach a maximum serum concentration in approximately 6.5 hours after administration. This is substantially longer than immediate-release Prednisone which reaches peak concentrations within 2 hours.
Tips to expedite clearance of Prednisone from your system
If you’re hoping to clear Prednisone and prednisolone from your system as soon as possible, there may be some things you can do to expedite the process. That said, due to its short half-life, the drug should be out of systemic circulation within 24 hours of your final dose. Any of the tips listed below should be discussed with a medical professional prior to implementation.
- Complete discontinuation: The most obvious way to completely eliminate Prednisone from your body is to stop taking it. The longer you’ve remained off of the drug, the more likely it is to have been fully excreted. Understand that discontinuation should never be rushed and should always be monitored by a medical professional.
- CYP3A4 inducers: Taking a drug that acts as a CYP3A4 inducer theoretically could ensure optimal metabolism speed of prednisolone. Since Prednisone has a short half-life, taking a CYP3A4 inducer to speed up clearance is probably unnecessary. Assuming you get medical approval to take a CYP3A4 inducer – realize that clearance speed may be enhanced.
- Acidify urinary pH: To ensure the fastest possible systemic clearance of Prednisone, prednisolone, and other metabolites – manipulating urinary pH may be helpful. The more acidic your urine (low pH), the less likely you’ll be to reabsorb prednisolone metabolites prior to excretion. If you have a highly alkaline (high pH) urine, acidification could significantly reduce clearance time.
- Stay hydrated: It may be helpful to maintain adequate hydration after you’ve stopped Prednisone if you want to ensure a fast excretion time. Hydration increases urinary flow rate, which is known to have a slight effect on clearance speed. If you are dehydrated, drinking more water should help you excrete prednisone quicker.
How long has Prednisone stayed in your system after stopping?
If you’ve stopped using Prednisone, share a comment regarding how long you think it stayed in your system after your final dose. Do you think that the drug (and its metabolites) are mostly excreted within 24 hours after your last dose? If you believe that Prednisone stays in your system for much longer than is suggested in medical reports, do you have any credible scientific evidence to support your claims?
Many people mistakenly believe that since Prednisone’s side effects linger after stopping, that the drug must still be in their system. In reality, the side effects are lingering because of the potent physiological effects that were exerted when Prednisone was in the body – not because it is still present. Think of Prednisone as analogous to a tornado going through a city and wreckage as lingering side effects.
Even though the tornado has passed and is gone (Prednisone is out of the system), the deleterious effects take awhile before they are corrected. In other words, after stopping Prednisone, it takes time for the wreckage to get fixed (adverse effects to subside). Know that for most people, Prednisone should be out of the body within a day or two of stopping.