Prednisone
Prednisone is a synthetic corticosteroid medication and prodrug that is metabolized in the liver to its active form, prednisolone, which provides potent anti-inflammatory and immunosuppressive effects by mimicking the actions of the naturally occurring hormone cortisol.[1][2] With the chemical formula C21H26O5, it belongs to the glucocorticoid class and is commonly prescribed under brand names such as Deltasone or Rayos.[1] Developed in the mid-20th century amid advancements in adrenal hormone research, prednisone was first isolated and identified in 1950 by Arthur Nobile using microbiological oxidation of cortisone with the bacterium Corynebacterium simplex, with the first commercially feasible synthesis reported in 1954.[1][3] It received U.S. Food and Drug Administration (FDA) approval on February 21, 1955, as an oral anti-inflammatory and immunosuppressive agent.[1] This approval followed the broader discovery of corticosteroids in the 1940s, including cortisone, which earned researchers Philip S. Hench, Edward C. Kendall, and Tadeusz Reichstein the 1950 Nobel Prize in Physiology or Medicine for their work on adrenal hormones and their therapeutic applications.[4][5] Prednisone's mechanism of action involves binding to intracellular glucocorticoid receptors, which translocate to the nucleus to regulate gene expression, inhibiting the production of pro-inflammatory mediators like prostaglandins and cytokines while promoting anti-inflammatory proteins and inducing apoptosis in certain immune cells.[2] It is rapidly absorbed after oral administration, reaching peak plasma concentrations in about 2 hours for immediate-release formulations, and is primarily excreted by the kidneys after hepatic metabolism.[2][1] The drug is indicated for a wide array of conditions, including endocrine disorders (such as adrenal insufficiency), rheumatic diseases (like rheumatoid arthritis), allergic reactions, dermatologic issues, asthma exacerbations, inflammatory bowel diseases (ulcerative colitis and Crohn's disease), systemic lupus erythematosus, multiple sclerosis relapses, and certain hematologic or neoplastic disorders.[6][2][7] Off-label uses extend to conditions like giant cell arteritis and severe COVID-19 cases requiring immunosuppression.[2] Available in tablet, delayed-release tablet, and oral solution forms, it is typically dosed at 5 to 60 mg daily for adults, adjusted based on the specific condition and patient response, and should be taken with food to minimize gastrointestinal upset.[6][2]Overview
Description
Prednisone is a synthetic glucocorticoid corticosteroid that serves as a prodrug, being biologically inert until metabolized in the liver to its active form, prednisolone.[2] It belongs to the corticosteroid family, which mimics the physiological effects of cortisol, the primary glucocorticoid hormone produced by the adrenal cortex.[2] This classification underscores its role in modulating immune responses through glucocorticoid receptor binding.[1] The molecular formula of prednisone is C21H26O5.[1] It appears as an odorless white crystalline powder and exhibits limited solubility in water, being very slightly soluble therein, while showing greater solubility in organic solvents such as alcohol (1 g in 150 mL) and chloroform (1 g in 200 mL).[1] Prednisone possesses notable immunosuppressive and anti-inflammatory properties, making it a key agent in therapeutic contexts requiring modulation of inflammatory processes.[1][2]Forms and Administration
Prednisone is available in several pharmaceutical forms to accommodate different patient needs and treatment requirements. The most common formulations include oral tablets in strengths ranging from 1 mg to 50 mg, such as 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg, and 50 mg tablets for immediate-release administration.[8] Oral solutions are also widely used, including a standard solution of 5 mg per 5 mL and a concentrate of 5 mg per 1 mL, which allow for precise dosing in patients who have difficulty swallowing tablets.[8][2] Delayed-release formulations provide an alternative for conditions requiring sustained effects, such as rheumatoid arthritis. In the United States, Rayos is a delayed-release tablet available in 1 mg, 2 mg, and 5 mg strengths, designed to release the active substance approximately 4 hours after ingestion to align with the body's natural cortisol rhythm.[9] In Europe, Lodotra is a similar modified-release tablet approved specifically for rheumatoid arthritis, releasing prednisone with a delay of about 4 to 6 hours post-intake to minimize early-morning symptoms.[10] For acute or severe cases where rapid systemic effects are needed, intravenous formulations of equivalent corticosteroids, such as methylprednisolone, are used, though oral routes predominate in most scenarios.[2] The primary route of administration for prednisone is oral, offering rapid absorption with a bioavailability of approximately 70% to 90% after ingestion, as it is converted to the active metabolite prednisolone in the liver.[11] Intravenous administration of equivalent corticosteroids is reserved for severe acute conditions to bypass gastrointestinal absorption and achieve immediate effects.[2] General administration guidelines emphasize patient comfort and efficacy. Prednisone should be taken with food or milk to minimize gastrointestinal upset, such as nausea or irritation.[2][12] Morning dosing is recommended, ideally before 9:00 AM, to mimic the natural diurnal variation of cortisol and reduce the risk of adrenal suppression.[2] Delayed-release tablets like Rayos or Lodotra must be swallowed whole and not crushed, divided, or chewed to preserve their timed-release mechanism.[9][12] Tapering protocols are essential when discontinuing prednisone after prolonged use to prevent adrenal insufficiency and withdrawal symptoms. Doses are gradually reduced over days to weeks, depending on the duration and intensity of therapy, often using therapy packs that provide pre-packaged decreasing strengths for structured withdrawal.[2][8] This approach allows the body's adrenal glands to resume normal function safely.[12]Medical Uses
Indications
Prednisone is approved by the U.S. Food and Drug Administration (FDA) for the treatment of a wide range of inflammatory, allergic, and autoimmune conditions due to its potent anti-inflammatory and immunosuppressive effects.[13] These indications span multiple organ systems and are supported by its role in suppressing immune-mediated damage.[2] In endocrine disorders, prednisone is indicated for primary or secondary adrenocortical insufficiency, congenital adrenal hyperplasia, hypercalcemia associated with cancer, and nonsuppurative thyroiditis, where it serves as replacement or supportive therapy to manage hormone imbalances.[13] For rheumatic disorders, it is used in conditions such as rheumatoid arthritis (including juvenile forms), psoriatic arthritis, ankylosing spondylitis, acute gouty arthritis, and various forms of bursitis or tenosynovitis, with ACR guidelines, including the 2021 RA guideline and 2025 SLE guideline, recommending its short-term use to control flares in rheumatoid arthritis and systemic lupus erythematosus (SLE) while transitioning to disease-modifying agents.[13][14][15] Collagen diseases like systemic lupus erythematosus, dermatomyositis (polymyositis), and acute rheumatic carditis also benefit from prednisone to reduce systemic inflammation.[13] Dermatologic diseases treated with prednisone include severe psoriasis, pemphigus, exfoliative dermatitis, and severe erythema multiforme (Stevens-Johnson syndrome), where it rapidly controls widespread skin inflammation.[13] Allergic states such as bronchial asthma, seasonal allergic rhinitis, atopic dermatitis, and drug hypersensitivity reactions are managed with prednisone to alleviate acute symptoms.[13] Ophthalmic diseases like uveitis, keratitis, optic neuritis, and allergic conjunctivitis respond to its anti-inflammatory action in ocular tissues.[13] Respiratory diseases, including symptomatic sarcoidosis, aspiration pneumonitis, and exacerbations of chronic obstructive pulmonary disease (COPD), are indications where prednisone reduces airway inflammation.[13][2] Hematologic disorders such as idiopathic thrombocytopenic purpura, acquired hemolytic anemia, and certain congenital anemias are treated with prednisone to modulate immune destruction of blood cells.[13] In neoplastic diseases, it provides palliative management for leukemias and lymphomas in adults and acute leukemia in children, often as an adjunct to chemotherapy.[13] Edematous states like nephrotic syndrome (idiopathic or lupus-related) use prednisone to induce remission of proteinuria.[13] Gastrointestinal diseases including ulcerative colitis and regional enteritis (Crohn's disease) are FDA-approved indications, though guidelines emphasize its role in induction of remission.[13] Off-label uses of prednisone are common and include management of inflammatory bowel disease flares, such as moderate-to-severe Crohn's disease and ulcerative colitis, where clinical guidelines recommend it as a bridge to steroid-free maintenance therapy.[16] In multiple sclerosis, prednisone is used off-label for acute relapses to accelerate recovery, often as an oral equivalent to intravenous methylprednisolone per guidelines from the American Academy of Neurology and NICE.[17] For organ transplant rejection prevention, prednisone is frequently employed off-label in immunosuppressive regimens, particularly in the early post-transplant period, combined with calcineurin inhibitors and other agents to minimize acute rejection risk.[18] In autoimmune conditions, prednisone often plays a role in combination therapies with disease-modifying antirheumatic drugs or biologics, as endorsed by ACR guidelines for optimizing efficacy while minimizing long-term exposure.[15] Off-label uses also extend to giant cell arteritis, where high-dose prednisone is used to rapidly reduce inflammation and prevent vision loss.[19]Dosage
Prednisone dosing is individualized based on the patient's condition, response, and risk factors, with the goal of using the lowest effective dose to minimize adverse effects. For adults, the initial oral dose typically ranges from 5 to 60 mg per day, administered as a single dose in the morning or divided doses with food to reduce gastrointestinal irritation. Maintenance doses are tapered to the lowest effective level, often 5 mg per day or less for chronic use.[2][20] In children, dosing is weight-based, generally ranging from 0.05 to 2 mg/kg per day orally, divided into one to four doses, with careful monitoring to avoid growth suppression. For example, in acute asthma exacerbations, adults may receive 40 to 60 mg per day orally for 3 to 10 days, while children are dosed at 1 to 2 mg/kg per day (maximum 60 mg) for a similar duration. In nephrotic syndrome, initial dosing for children is 60 mg/m² per day or 2 mg/kg per day (maximum 60 mg) orally until remission, followed by tapering. High-dose therapy often requires gradual tapering over weeks to months to prevent adrenal insufficiency, such as reducing by 2.5 to 5 mg every 1 to 2 weeks once stable.[2][20][21][22] Dose adjustments are necessary for certain populations. No specific modifications are required for renal impairment, though monitoring is advised due to potential fluid retention. In hepatic impairment, such as cirrhosis, bioavailability may increase, necessitating cautious dosing and closer observation without routine reduction. For elderly patients, the lowest effective dose is recommended, with attention to decreased renal function and comorbidities that heighten side effect risks. Prednisone is classified as pregnancy category C; it should be used only if the benefit outweighs potential risks, with doses preferably below 20 mg per day to limit fetal exposure, as higher amounts may increase preterm birth risk.[2][9][23] Monitoring involves regular assessments of treatment efficacy and adverse effects, including blood pressure, glucose levels, electrolytes, and bone mineral density, particularly during long-term use. Emphasis is placed on achieving the lowest effective dose and shortest duration, as per 2025 updates from sources like the National Institutes of Health and KDIGO guidelines, which advocate minimizing cumulative exposure to reduce complications. Patients on prolonged therapy should undergo hypothalamic-pituitary-adrenal axis evaluation, such as morning cortisol testing, before tapering.[2][22]Contraindications and Interactions
Contraindications
Prednisone is contraindicated in patients with systemic fungal infections due to the risk of exacerbating the infection through immunosuppression.[2] It is also contraindicated in individuals with known hypersensitivity to prednisone or any of its components, as this can lead to severe allergic reactions.[9] Additionally, administration of live or live attenuated vaccines is contraindicated during prednisone therapy, particularly at immunosuppressive doses, because the vaccine virus may replicate uncontrollably in immunocompromised patients.[24] Relative contraindications for prednisone include active untreated infections such as tuberculosis or viral infections, where the drug's immunosuppressive effects could worsen the condition.[25] It should be used with caution in patients with peptic ulcer disease, as corticosteroids may increase the risk of gastrointestinal perforation or hemorrhage. Other relative contraindications encompass uncontrolled diabetes mellitus, due to prednisone's potential to elevate blood glucose levels; osteoporosis, which may be aggravated by bone density loss; psychosis or other psychiatric disorders, potentially exacerbated by mood alterations; and recent myocardial infarction, where fluid retention could strain cardiac function.[25] In special populations, prednisone should be avoided during pregnancy if possible, as it is classified as FDA pregnancy category C, with animal studies showing adverse fetal effects and potential human teratogenic risks such as cleft palate at high doses in the first trimester, though benefits may outweigh risks in certain cases.[26] For breastfeeding individuals, caution is advised due to minimal excretion of prednisone into breast milk, but infants should be monitored for potential adrenal suppression or growth issues with prolonged high-dose maternal use.[27] Corticosteroids like prednisone carry warnings for increased susceptibility to new infections in immunocompromised patients, including risks of opportunistic infections, though no specific black box warning update was issued by the FDA in 2025.[9]Drug Interactions
Prednisone, a glucocorticoid, undergoes metabolism primarily via the cytochrome P450 3A4 (CYP3A4) enzyme system, leading to significant interactions with drugs that inhibit or induce this pathway. CYP3A4 inhibitors such as ketoconazole and clarithromycin can increase prednisone plasma levels by slowing its breakdown, potentially heightening the risk of steroid-related adverse effects like immunosuppression or Cushing's syndrome; dose reduction of prednisone may be necessary in such cases. Conversely, CYP3A4 inducers like rifampin and phenytoin accelerate prednisone metabolism, reducing its efficacy and necessitating higher doses to maintain therapeutic levels.[2] Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, interact with prednisone by increasing the risk of gastrointestinal ulceration and bleeding due to their combined effects on mucosal protection and platelet function; co-administration should be monitored closely, with proton pump inhibitors often recommended for gastroprotection. Anticoagulants like warfarin can have inconsistent effects on international normalized ratio (INR) when combined with prednisone, as steroids may alter vitamin K metabolism or protein binding; frequent INR monitoring and dose adjustments are essential to prevent thrombosis or hemorrhage. In patients with diabetes, prednisone exacerbates hyperglycemia by promoting gluconeogenesis and insulin resistance, potentially requiring intensified antidiabetic therapy such as increased insulin doses; regular blood glucose monitoring is advised during concurrent use. Live vaccines, including those for varicella or measles, exhibit reduced immunogenicity with prednisone due to its immunosuppressive properties, and administration should be avoided or timed carefully to minimize infection risk.[2][28][29] Among moderate interactions, antihypertensives such as ACE inhibitors may have blunted effects from prednisone-induced fluid retention and sodium retention, warranting blood pressure monitoring and possible diuretic addition. Diuretics, particularly loop diuretics like furosemide, combined with prednisone can lead to electrolyte imbalances, including hypokalemia, due to additive potassium loss; serum electrolyte levels should be checked regularly. Digoxin toxicity risk increases with prednisone through hypokalemia-induced arrhythmias, especially in patients with heart failure; electrocardiogram monitoring and potassium supplementation may be required.[2][28] Food and herbal interactions include grapefruit juice, which inhibits CYP3A4 and elevates prednisone concentrations similar to pharmaceutical inhibitors, advising avoidance during treatment. St. John's wort, an herbal CYP3A4 inducer, decreases prednisone efficacy by enhancing its metabolism; patients should discontinue it prior to starting prednisone. Management strategies generally involve dose adjustments based on clinical response, therapeutic drug monitoring where applicable (e.g., INR for anticoagulants or glucose for antidiabetics), and patient education on avoiding interacting substances.[29][2] Recent data highlight interactions with COVID-19 antivirals; for instance, Paxlovid (nirmatrelvir/ritonavir) significantly increases prednisone exposure via ritonavir's potent CYP3A4 inhibition, potentially amplifying steroid side effects over the 5-day treatment course, with recommendations for prednisone dose reduction or close monitoring in co-therapy scenarios.[30][31]Adverse Effects
Short-term Effects
Short-term use of prednisone, typically defined as courses lasting less than two weeks, commonly leads to increased appetite and subsequent weight gain, affecting a notable portion of patients due to its influence on metabolism and fluid balance. Insomnia is another frequent complaint, often exacerbated by evening dosing, while gastrointestinal upset manifests as nausea, indigestion, or abdominal discomfort, occurring in up to 27% of individuals on high-dose short-term regimens.[32][33][34] Mood alterations, including euphoria, irritability, or agitation, are prevalent short-term effects, with behavioral changes reported during acute therapy, particularly in pediatric patients at approximately 4.7%; severe manifestations like acute psychosis occur less frequently at doses exceeding 20 mg/day. Major acute effects encompass hyperglycemia, which can elevate blood glucose levels and cause symptoms such as increased thirst and urination, alongside hypertension and fluid retention leading to edema in the extremities. Prednisone also heightens susceptibility to infections through transient immunosuppression, with sepsis risk rising up to fivefold within 30 days of initiation in some populations. Acute myopathy, characterized by muscle weakness or pain, may develop rapidly at high doses, though it remains uncommon.[35][36][33][37][34][38] These short-term effects are generally reversible upon discontinuation, distinguishing them from cumulative long-term complications. Management focuses on symptomatic relief and minimization strategies, such as administering prednisone with food or milk to mitigate gastrointestinal irritation, adopting a low-sodium diet to reduce fluid retention, and monitoring blood glucose and pressure in at-risk patients; dose reduction or tapering is recommended if side effects impair tolerability, while short courses help limit overall exposure.[32][34][37][39][40]Long-term Effects
Prolonged use of prednisone, a glucocorticoid, leads to significant metabolic disturbances, including osteoporosis characterized by substantial bone density loss and increased fracture risk. At daily doses exceeding 20 mg, patients may experience an annual spinal bone density reduction of 5-15%, with the highest rates occurring in the first year of therapy, elevating the likelihood of vertebral and hip fractures by up to fivefold. Adrenal suppression is another key metabolic effect, where chronic exposure inhibits the hypothalamic-pituitary-adrenal axis, potentially resulting in insufficient cortisol production upon dose reduction. Features of Cushing's syndrome, such as moon face, buffalo hump, and central obesity, also emerge from sustained high-dose use, contributing to metabolic syndrome components like hyperglycemia and dyslipidemia. Cardiovascular risks escalate with long-term prednisone therapy, primarily through induced hypertension and accelerated atherosclerosis. Even low doses (e.g., 5 mg daily) can double the absolute risk of fatal and nonfatal cardiovascular events, including myocardial infarction and heart failure, after one year, due to effects on lipid profiles and vascular fibrosis. Ocular complications are prominent, with prolonged therapy significantly increasing the incidence of posterior subcapsular cataracts, with risks up to several-fold higher, and inducing glaucoma through elevated intraocular pressure, particularly in susceptible individuals. Dermatological changes, such as skin thinning and easy bruising, arise from collagen degradation, often persisting even after discontinuation if use exceeds several months. In pediatric patients, long-term prednisone administration suppresses linear growth by interfering with growth hormone pathways, with cumulative doses correlating to reduced height velocity, especially in those receiving more than four relapse treatments. There is also evidence of heightened malignancy risk among long-term users, potentially linked to immunosuppression, though risks vary by cancer type. To mitigate these effects, strategies include maintaining the lowest effective dose, supplementing with calcium (1,000-1,200 mg daily) and vitamin D (800-1,000 IU daily) to counteract bone loss, and using bisphosphonates like alendronate for high-risk patients. Current guidelines recommend baseline and periodic DEXA scans for bone density monitoring in adults on doses ≥7.5 mg daily for over three months, with follow-up every 1-2 years to guide interventions. According to the 2024 joint European Society of Endocrinology and Endocrine Society guidelines, baseline and periodic assessments are recommended to manage these risks.[41]Withdrawal and Dependency
Prednisone, a synthetic glucocorticoid, can lead to physiological dependency through suppression of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in secondary adrenal insufficiency upon abrupt discontinuation. This suppression occurs because exogenous glucocorticoids like prednisone inhibit the production of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), reducing endogenous cortisol synthesis by the adrenal glands.[41][42] Withdrawal symptoms from prednisone discontinuation mimic those of adrenal insufficiency and may include fatigue, joint pain, fever, hypotension, and exacerbation of the underlying disease; in severe cases, this can progress to an Addisonian crisis characterized by profound hypotension, hyponatremia, and potentially life-threatening shock. These symptoms typically emerge when tapering below physiologic doses (around 5 mg/day prednisone equivalent) and can overlap with glucocorticoid withdrawal syndrome, which arises from the body's adjustment to reduced steroid levels.[43][44] Risk factors for significant HPA axis suppression and withdrawal include treatment duration exceeding 3-4 weeks and daily doses greater than 20 mg prednisone, though even lower doses (e.g., 5 mg/day) over prolonged periods can pose risks in susceptible individuals. Management involves gradual tapering to allow HPA axis recovery, such as reducing the dose by 5-10 mg per week for high-dose regimens (>20-40 mg/day) until reaching physiologic levels (4-6 mg/day), followed by slower decrements of 1 mg per month. During stressors like surgery or acute illness, stress-dose steroids (e.g., hydrocortisone 50-100 mg IV) are administered to prevent crisis.[45][41][42] True psychological addiction to prednisone is rare, but behavioral reliance can develop due to its mood-elevating effects like euphoria, with case reports documenting tolerance, withdrawal anxiety, and compulsive seeking in a minority of patients, often those with underlying psychiatric conditions. The 2024 Endocrine Society and European Society of Endocrinology joint guidelines emphasize patient education on these risks and multidisciplinary monitoring to facilitate safe withdrawal without psychological distress.[46][42][41]Pharmacology
Mechanism of Action
Prednisone is a synthetic glucocorticoid prodrug that is biologically inactive until converted to its active metabolite, prednisolone, primarily in the liver via reduction by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1).[47][2] This conversion is essential for its therapeutic activity, as prednisolone is the form that exerts pharmacological effects.[48] Once activated, prednisolone diffuses across cell membranes and binds to the intracellular glucocorticoid receptor (GR), forming a steroid-receptor complex that translocates to the nucleus.[48][2] There, the complex acts as a transcription factor, either enhancing the expression of anti-inflammatory genes (e.g., lipocortin-1) or repressing pro-inflammatory ones through interactions with DNA response elements.[49] A key anti-inflammatory mechanism involves the inhibition of phospholipase A2, which reduces the release of arachidonic acid from membrane phospholipids, thereby decreasing the synthesis of inflammatory mediators such as prostaglandins, leukotrienes, and cytokines including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α).[2][50] The immunosuppressive effects of prednisone stem from prednisolone's ability to induce apoptosis in T-lymphocytes, impair B-cell receptor signaling to reduce antibody production, and alter neutrophil dynamics by promoting demargination from the marginal pool into circulation while inhibiting their migration to inflammatory sites.[51][52][53] These actions contribute to overall immune modulation, with a central pathway being the transrepression of nuclear factor-kappa B (NF-κB), a pivotal transcription factor that drives the expression of numerous pro-inflammatory and immune-activating genes.[54][49] Glucocorticoid effects exhibit dose dependency, with genomic mechanisms—mediated by nuclear translocation and transcriptional changes—predominating at lower, physiological doses and requiring hours to manifest, while non-genomic effects, involving rapid membrane-associated signaling and protein interactions, become prominent at higher pharmacological doses for quicker onset of action.[55][56] This duality allows prednisone to address both acute and chronic inflammatory conditions effectively.[50]Pharmacokinetics
Prednisone, a synthetic glucocorticoid prodrug, is administered orally and exhibits rapid absorption from the gastrointestinal tract, with peak plasma concentrations (T_max) typically reached within 1 to 2 hours for immediate-release formulations.[2] Its bioavailability ranges from 70% to 90%, though this can vary slightly with formulation; food intake may delay absorption but does not significantly alter overall bioavailability.[57][48] Following absorption, prednisone is widely distributed throughout the body, with a volume of distribution of approximately 0.6 to 1.5 L/kg, reflecting its lipophilic nature that allows penetration into tissues.[58] It is highly bound to plasma proteins, primarily albumin and transcortin (corticosteroid-binding globulin), at 70% to 90%.[59] Prednisone and its active metabolite prednisolone cross the placenta, though placental metabolism limits fetal exposure, and they penetrate the blood-brain barrier to reach central nervous system tissues.[60] Prednisone undergoes rapid hepatic metabolism, primarily via conversion to its active form, prednisolone, through 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1); this biotransformation occurs in the liver and, to a lesser extent, other tissues.[48] Further metabolism of prednisolone involves cytochrome P450 3A4 (CYP3A4) enzymes, producing metabolites such as 6β-hydroxyprednisolone and 20α-dihydro-prednisolone, which are then conjugated to glucuronides or sulfates.[61] The plasma half-life of prednisone is 3 to 4 hours in adults, while that of prednisolone is 2 to 4 hours.[2] Elimination primarily occurs through renal excretion of inactive metabolites, with approximately 90% of the dose recovered in urine as conjugates; less than 5% is excreted unchanged.[62] In patients with hepatic impairment, such as cirrhosis, the half-life of both prednisone and prednisolone is prolonged due to reduced metabolic clearance and conversion efficiency, potentially necessitating dose adjustments or preference for prednisolone.[63] In children, the half-life is shorter (1 to 2 hours) compared to adults (3 to 4 hours), reflecting faster metabolism; in neonates, it may vary due to developing enzyme systems, though therapeutic drug monitoring is rarely required except in complex cases like organ transplantation.[2]Pharmacodynamics
Prednisone, once converted to its active form prednisolone, exerts systemic effects that mimic those of endogenous cortisol, influencing carbohydrate, protein, and lipid metabolism as well as electrolyte balance. It promotes gluconeogenesis and hyperglycemia by enhancing hepatic glucose production while inhibiting peripheral glucose uptake, leading to elevated blood sugar levels. In protein metabolism, it induces catabolism, particularly in muscle tissue, resulting in negative nitrogen balance. For lipids, it stimulates lipolysis and redistribution of fat, contributing to dyslipidemia. Regarding electrolytes, prednisone causes sodium retention and potassium excretion, which can disrupt fluid balance through mineralocorticoid-like activity, especially at higher doses.[64] The physiological responses to prednisone are dose-dependent, with low doses (typically 5-20 mg/day) primarily eliciting anti-inflammatory effects by suppressing cytokine production and immune cell migration, whereas higher doses (≥40 mg/day) produce profound immunosuppressive actions, including inhibition of T-cell proliferation and antibody synthesis. Chronic administration leads to tolerance development through glucocorticoid receptor downregulation, reducing cellular sensitivity and necessitating dose adjustments or tapering to maintain efficacy.[64][65] Key biomarkers of prednisone's pharmacodynamic effects include alterations in white blood cell counts, such as lymphopenia due to redistribution and apoptosis of lymphocytes, and neutrophilia from demargination and reduced neutrophil apoptosis, often resulting in an elevated neutrophil-to-lymphocyte ratio. It also reduces inflammatory markers like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, reflecting decreased systemic inflammation.[2][64] In terms of comparative potency, prednisone is approximately 4-5 times more potent than cortisol (hydrocortisone) on a glucocorticoid basis, requiring about one-fourth the dose for equivalent anti-inflammatory effects. Relative to dexamethasone, it is about one-fourth to one-fifth as potent. The following table summarizes standard glucocorticoid equivalencies for anti-inflammatory dosing:| Glucocorticoid | Equivalent Dose (mg) | Relative Potency (vs. Cortisol) |
|---|---|---|
| Cortisol | 20 | 1 |
| Prednisone | 5 | 4 |
| Dexamethasone | 0.75 | 25-30 |