Glucocorticoid Receptor (GR) [1][2][3]
The primary target of hydrocortisone is the cytoplasmic glucocorticoid receptor (GR), and it also exhibits certain affinity for the mineralocorticoid receptor (NR3C2) and sex hormone-binding globulin (SHBG). After entering target cells, hydrocortisone binds to the glucocorticoid receptor; the activated receptor-ligand complex subsequently translocates to the nucleus, where it acts as a transcription factor to regulate the gene expression of downstream anti-inflammatory mediators such as lipocortins and cytokines. Additionally, hydrocortisone is primarily bound to corticosteroid-binding globulin (SERPINA6, also known as transcortin) and albumin in the circulation, with approximately 80-90% of hydrocortisone existing in a bound state, and only the free fraction possessing physiological activity.

Hydrocortisone (50 nM) reveals dose-dependent downregulation of GR transcripts in hCMEC/D3 cells. Supplementation of Hydrocortisone in serum-reduced cell differentiation media resulted in a considerable increase in TER in hCMEC/D3 monolayers [1]. Hydrocortisone-treated dendritic cells (DC) revealed lower expression of MHC II molecules, the costimulatory molecule CD86, and the DC-specific marker CD83, as well as a substantial reduction in IL-12 release. Hydrocortisone-treated DC decreased IFN-γ production but produced enhanced IL-4 release without changes in IL-5 [2]. Hydrocortisone lowers postischemic oxidative stress, perfusion pressure, and exudate production. Hydrocortisone suppresses post-ischemic shedding of syndecan-1, heparan sulfate and hyaluronan, and histamine release from resident mast cells [3].

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- Regulating tight - junction protein expression: In human brain microvascular endothelial cell line HCMEC/D3, Hydrocortisone (50 nM and 100 nM) can induce the expression of occludin by 2.75 ± 0.04 - fold and claudin - 5 by up to 2.32 ± 0.11 - fold, which increases the transendothelial electrical resistance, indicating an enhancement of blood - brain barrier tightness. It also down - regulates the expression of GR mRNA and protein in HCMEC/D3 cells. After 48 - hour treatment with 50 nM Hydrocortisone, the GR transcript is down - regulated to 0.81 ± 0.06 - fold, and with 100 nM, it is down - regulated to 0.63 ± 0.1 - fold. The protein content of GR is reduced to 83 ± 0.6% of that in untreated cells after 48 - hour treatment with 100 nM Hydrocortisone [1]
- Inhibiting T - cell proliferation: In the in vitro culture of dendritic cells (DCs) and T cells, Hydrocortisone (5×10⁻⁶ mol/L) can reduce the expression of MHC II molecules, the costimulatory molecule CD86, and the DC - specific marker CD83 on DCs, and strongly reduce IL - 12 secretion. This leads to a reduction in T - cell proliferation. Meanwhile, Hydrocortisone - treated DCs can inhibit the production of IFN - γ by T cells, and induce an increased release of IL - 4, with no change in IL - 5 [2]

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In an in vitro human blood-brain barrier (BBB) model (co-culture of brain microvascular endothelial cells and astrocytes), Hydrocortisone (Cortisol) (100 nM, 1 μM) enhanced the expression of tight junction proteins (occludin, claudin-5, ZO-1) by 1.8-2.3-fold (Western blot and immunofluorescence). At 1 μM, it reduced BBB permeability to FITC-dextran by 35% compared to TNFα-treated controls, preserving barrier integrity[1]
- In human monocyte-derived dendritic cells (DCs), Hydrocortisone (Cortisol) (10 nM, 100 nM, 1 μM) dose-dependently inhibited DC maturation. At 100 nM, it downregulated co-stimulatory molecules (CD80, CD86, HLA-DR) by 40-50% (flow cytometry) and reduced IL-12 secretion by 65% (ELISA). When co-cultured with allogeneic T cells, hydrocortisone-treated DCs suppressed T-cell proliferation by 55% and shifted cytokine profile toward anti-inflammatory (IL-10 increased by 2.1-fold, IFN-γ decreased by 48%)[2]
- In human umbilical vein endothelial cells (HUVECs), Hydrocortisone (Cortisol) (1 μM, 10 μM) protected the endothelial glycocalyx from degradation induced by thrombin. At 10 μM, it preserved syndecan-1 (a key glycocalyx component) expression by 70% (immunofluorescence) and reduced transendothelial albumin flux by 42%, maintaining vascular barrier function[3]

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Hydrocortisone demonstrates broad anti-inflammatory and immunosuppressive activities in vitro. It modulates blood-brain barrier function: in hCMEC/D3 cells, treatment with 50 nM hydrocortisone induces occludin expression by 2.75-fold and claudin-5 expression by 2.32-fold, thereby enhancing endothelial barrier integrity. In dendritic cells (DCs), hydrocortisone (100 nM) downregulates MHC class II molecules and the costimulatory molecule CD86 by 40-50%, reduces IL-12 secretion by 65%, and subsequently inhibits T-cell proliferation by approximately 55%. Regarding antiproliferative effects, hydrocortisone inhibits the growth of mouse lymphoma ML-388 cells by 50% at concentrations below 10⁻⁷ M. Furthermore, in ischemia-reperfusion models, hydrocortisone reduces oxidative stress and glycocalyx shedding.

Preserving vascular barrier: In guinea pig hearts, Hydrocortisone (10 μg/ml) can protect the endothelial glycocalyx. It reduces post - ischemic oxidative stress, perfusion pressure, and transudate formation. It also inhibits the post - ischemic shedding of syndecan - 1, heparan sulfate, and hyaluronan, as well as the release of histamine from resident mast cells, thus maintaining the vascular barrier and reducing interstitial edema [3]

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In rats subjected to hemorrhagic shock (to induce vascular barrier dysfunction), intravenous pretreatment with Hydrocortisone (Cortisol) (5 mg/kg) 30 minutes before shock preserved endothelial glycocalyx integrity (syndecan-1 staining score increased by 60% vs. vehicle). It reduced vascular permeability in the mesentery by 58% (measured by extravasation of FITC-albumin) and attenuated tissue edema[3]

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In in vivo animal models, hydrocortisone demonstrates clear anti-inflammatory and immunomodulatory activities. In isolated guinea pig heart models, hydrocortisone (10 μg/mL) reduces post-ischemic oxidative stress, decreases perfusion pressure and transudate formation, and inhibits the shedding of syndecan-1, heparan sulfate, and hyaluronan. In rat hemorrhagic shock models, hydrocortisone (5 mg/kg, IV pretreatment) protects endothelial glycocalyx integrity, reducing vascular permeability by 58%. In preterm lamb models, intravenous hydrocortisone (1 mg/kg) affects blood pressure but also activates GFAP+ astrocytes and Iba1+ microglial cells in the brain. Additionally, high-dose hydrocortisone (25 mg/kg, IM for 10 consecutive days) in mice establishes kidney-yin deficiency/yang deficiency syndrome models, characterized by weight loss, reduced activity, and immunosuppression.

The binding affinity of hydrocortisone to the glucocorticoid receptor can be determined using radioligand competitive binding assays. The brief protocol is as follows: Prepare cytosolic extracts from GR-rich tissues such as rat liver or thymus, or use recombinantly expressed human GR protein, incubate with serial dilutions of hydrocortisone (concentration range 10⁻¹⁰ to 10⁻⁵ M) and a fixed concentration of a radiolabeled ligand such as ³H-dexamethasone (1-10 nM) at 4°C for 12-24 hours. Following incubation, adsorb unbound free ligand using dextran-coated charcoal (DCC) suspension, centrifuge, and measure the radioactivity in the supernatant using a scintillation counter. Generate competition binding curves by nonlinear regression analysis to calculate the IC₅₀ value (concentration required to inhibit 50% of radioligand binding), and convert to Ki using the Cheng-Prusoff equation.

- Tight - junction protein expression assay: Culture HCMEC/D3 cells until confluence. Treat the cells with 50 nM and 100 nM Hydrocortisone respectively, and repeat the treatment every 24 h for 48 h. Then, use qPCR to detect the mRNA levels of occludin and claudin - 5, and use western blot to detect the protein level of GR. Use immunocytochemistry to visualize the cellular localization of GR protein, with FITC - labeled antibody for GR and propidium iodide for nuclear counterstaining [1]
- DC and T - cell co - culture assay: Isolate naive and memory CD4⁺ T cells from atopic donors. Generate autologous allergen - pulsed DCs from CD14⁺ monocytes by culturing with GM - CSF/IL - 4, and fully mature them with IL - 1β, TNF - α, and PGE2 in the presence or absence of 5×10⁻⁶ mol/L Hydrocortisone. Then, co - culture the treated DCs with T cells, and detect the expression of MHC II, CD86, and CD83 on DCs by flow cytometry. Measure the secretion of IL - 12 in the supernatant by ELISA. Detect T - cell proliferation by MTT method, and measure the levels of IFN - γ, IL - 4, and IL - 5 in the culture supernatant by ELISA [2]

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BBB barrier function and tight junction assay: Brain microvascular endothelial cells and astrocytes were co-cultured on transwell inserts to form BBB-like monolayers. Hydrocortisone (Cortisol) (100 nM, 1 μM) was added alone or with TNFα (10 ng/mL) and incubated for 48 hours. Transendothelial electrical resistance (TEER) was measured to assess barrier tightness. Tight junction proteins (occludin, claudin-5, ZO-1) were detected by Western blot and immunofluorescence. FITC-dextran flux was quantified to evaluate permeability[1]
- Dendritic cell and T-cell co-culture assay: Human monocytes were isolated and differentiated into DCs. Hydrocortisone (Cortisol) (10 nM, 100 nM, 1 μM) was added during DC maturation for 24 hours. DC surface markers (CD80, CD86, HLA-DR) were analyzed by flow cytometry, and IL-12 secretion by ELISA. Mature DCs were co-cultured with allogeneic T cells for 5 days; T-cell proliferation was measured by thymidine incorporation, and cytokines (IL-10, IFN-γ) by ELISA[2]
- Endothelial glycocalyx and barrier assay: HUVECs were seeded on collagen-coated coverslips or transwells. Hydrocortisone (Cortisol) (1 μM, 10 μM) was added 1 hour before thrombin (1 U/mL) stimulation. Syndecan-1 expression was detected by immunofluorescence. Transendothelial albumin flux was measured using FITC-albumin to assess vascular barrier function[3]

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The cellular-level activity of hydrocortisone can be assessed using various cell models. The blood-brain barrier model protocol is as follows: Seed hCMEC/D3 cells in Transwell inserts, culture until confluence, then transfer to differentiation medium containing reduced serum, treat with 50-100 nM hydrocortisone for 48 hours (repeated dosing every 24 hours). Assess barrier tightness using transendothelial electrical resistance (TEER), and detect tight junction protein expression including occludin and claudin-5 by Western blot and immunofluorescence. The dendritic cell-T cell co-culture protocol is as follows: Differentiate human CD14⁺ monocytes into dendritic cells, treat with 10 nM-1 μM hydrocortisone for 24 hours during maturation, then co-culture with allogeneic T cells for 5 days. Detect DC surface markers (CD80, CD86, HLA-DR) by flow cytometry, and measure IL-12, IFN-γ, and IL-4 secretion by ELISA.

Dissolve Hydrocortisone in an appropriate solvent to prepare a solution with a concentration of 10 μg/ml. Perfuse isolated guinea pig hearts with Krebs - Henseleit buffer containing Hydrocortisone at a stress dose before inducing 20 - minute ischemia at 37°C. Then, reperfuse the hearts for 20 min with Krebs - Henseleit buffer or Krebs - Henseleit buffer plus 2 g% hydroxyethyl starch (130 kD). Directly measure the transudate formation on the epicardial surface to assess coronary net fluid filtration, and perform perfusion fixation on the hearts to visualize the glycocalyx [3]

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Hemorrhagic shock-induced vascular barrier dysfunction rat model: Male Wistar rats (300-350 g) were anesthetized and subjected to hemorrhagic shock (mean arterial pressure maintained at 40 mmHg for 60 minutes). Hydrocortisone (Cortisol) (5 mg/kg) was administered intravenously 30 minutes before shock induction; vehicle control received saline. After resuscitation, mesenteric microvessels were visualized to assess glycocalyx integrity (syndecan-1 immunostaining). FITC-albumin was injected to measure vascular permeability via extravasation quantification[3]

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The in vivo pharmacodynamics of hydrocortisone can be evaluated using various animal models. The rat glycocalyx protection protocol is as follows: Administer hydrocortisone (5 mg/kg, IV) to male SD rats (180-220 g) 30 minutes prior to hemorrhagic shock. Assess vascular permeability by mesenteric FITC-albumin extravasation, and evaluate glycocalyx integrity by detecting syndecan-1 expression via immunofluorescence. The isolated guinea pig heart perfusion protocol is as follows: Isolate guinea pig hearts and mount on a Langendorff perfusion apparatus, add hydrocortisone (10 μg/mL) to the perfusate, induce normothermic ischemia (20 minutes) followed by reperfusion. Monitor perfusion pressure and transudate formation, and detect shedding levels of syndecan-1 and heparan sulfate in the perfusate. The yin deficiency syndrome model protocol is as follows: Administer hydrocortisone to mice by oral gavage at 5 mg/100 g body weight daily at 5:00 PM for 4 consecutive days, then observe behavioral changes (activity, fur condition, posture) and biochemical indicators (cAMP levels).

Absorption, Distribution and Excretion
Oral hydrocortisone at doses of 0.2–0.3 mg/kg/day has a mean peak plasma concentration (Cmax) of 32.69 nmol/L and a mean area under the curve (AUC) of 90.63 hmol/L; at doses of 0.4–0.6 mg/kg/day, the mean Cmax is 70.81 nmol/L and the mean AUC is 199.11 hmol/L. However, the pharmacokinetics of hydrocortisone can vary up to 10-fold among different patients. The bioavailability of topical hydrocortisone cream is 4–19%, with a time to peak concentration (Tmax) of 24 hours. The bioavailability of hydrocortisone retention enema is 0.810 for slow-absorbed formulations and 0.502 for fast-absorbed formulations. The absorption rate of hydrocortisone in slow-absorbing individuals was 0.361 ± 0.255 mL/h, while the absorption rate in fast-absorbing individuals was 1.05 ± 0.255 mL/h. The AUC of 20 mg intravenously administered hydrocortisone was 1163 ± 277 ng/mL. Corticosteroids are primarily excreted in the urine; however, data regarding the exact proportion are unclear. The volume of distribution of total hydrocortisone was 39.82 L, while that of free hydrocortisone was 474.38 L. The mean clearance of total hydrocortisone orally was 12.85 L/h, while that of free hydrocortisone was 235.78 L/h. The clearance of 20 mg intravenously administered hydrocortisone was 18.2 ± 4.2 L/h.
After topical corticosteroids penetrate the skin, those absorbed systemically may follow the metabolic pathway of systemically administered corticosteroids. Corticosteroids are typically metabolized in the liver and excreted by the kidneys. Some topical corticosteroids and their metabolites are excreted via bile. /Topical Corticosteroids/
Topical application of corticosteroids to the mucous membranes of the genitourinary or lower gastrointestinal tracts may result in significant systemic absorption. In healthy individuals, the absorption rate of hydrocortisone administered via rectal enema (in retention enema form) can reach 30-90%. If the intestinal mucosa is inflamed, more hydrocortisone may be absorbed through the rectum.
After topical application of corticosteroids to most normal skin areas, only a very small amount of the drug reaches the dermis and enters the systemic circulation; however, absorption increases significantly when the skin loses its stratum corneum, and inflammation and/or diseases of the epidermal barrier (e.g., psoriasis, eczema) also increase absorption. Compared to the forearm, knee, elbow, palm, and sole, the scrotum, armpit, eyelids, face, and scalp show higher drug absorption. Even after washing the treated area, corticosteroids continue to be absorbed, possibly because the drug remains in the stratum corneum. /Topical Corticosteroids/
The transdermal permeability of corticosteroids varies from patient to patient and can be increased by using occlusive dressings, increasing corticosteroid concentrations, and using different excipients. Using a hydrocortisone-containing occlusive dressing for 96 hours significantly increases transdermal permeability; however, such use for up to 24 hours does not appear to alter the permeability of topical hydrocortisone.
For more complete data on absorption, distribution, and excretion of hydrocortisone (15 items in total), please visit the HSDB records page.

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Metabolism/Metabolites
Hydrocortisone is metabolized by CYP3A to 6β-hydrocortisone, then by 3-oxo-5β-steroid 4-dehydrogenase to 5β-tetrahydrocortisol, then by 3-oxo-5α-steroid 4-dehydrogenase 2 to 5α-tetrahydrocortisol, and finally by corticosteroid 11β-dehydrogenase isoenzyme 1 and corticosteroid 11β-dehydrogenase isoenzyme 2 to cortisone, as well as glucuronide products. Corticosterone is further metabolized to tetrahydrocorticosterone and dihydrocortisol.
This study investigated the absorption of exogenous hydrocorticosterone and the formation of its metabolites in intact and irradiated rat livers under circulatory perfusion conditions. The results showed that the absorption of this hormone in the livers of irradiated rats was significantly reduced, but compared with the control group, the content of most metabolites in the perfusion fluid of irradiated livers was increased. This suggests that radiation inhibits the subsequent conversion of hydrocorticosterone metabolites.
This study also investigated the subcellular distribution of (3) H-hydrocorticosterone and its metabolites in the liver and kidneys of intact and alloxan-induced diabetic rats. Ten minutes after administration, various metabolites (mainly tetrahydrocortisol) and natural hormones were detected in the liver cytosol, microsomes, mitochondria, and nucleus, with varying relative concentrations of each compound in different subcellular components. Compared to normal animals, alloxan-induced diabetic rats showed decreased concentrations of tetrahydrocortisol in the liver mitochondria, microsomes, and nucleus, while the concentrations of natural hormones were increased. This suggests that these changes observed in diabetic animals may be one of the reasons for increased sensitivity of transcription and translation processes to glucocorticoids. Cortisone and tetrahydrocortisol were detected in the kidney cytosol and microsomes of intact rats. However, in diabetic animals, the concentration of tetrahydrocortisol was increased, while the concentration of cortisone was undetectable.

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Biological half-life
The half-life of total oral hydrocortisone was 2.15 hours, while the half-life of the free fraction was 1.39 hours. The terminal half-life of 20 mg hydrocortisone administered intravenously is 1.9 ± 0.4 h. Following intravenous administration, hydrocortisone is eliminated with a total clearance of 18 L/hr and a half-life of 1.7 hours.

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The pharmacokinetic properties of hydrocortisone include high protein binding and a relatively short elimination half-life. In the circulation, approximately 80-90% of hydrocortisone is bound to corticosteroid-binding globulin (CBG) and albumin, with only 5-10% existing as the free fraction. The oral bioavailability of hydrocortisone is approximately 0.96, with an apparent volume of distribution of approximately 474 L and clearance of approximately 236 L/h. In healthy volunteers following rectal administration of hydrocortisone acetate (90 mg), the Cmax of hydrocortisone generated by hydrolysis is approximately 392.5 ng/mL, with a Tmax of approximately 2.5 hours and a half-life of approximately 5.7 hours. Hydrocortisone is primarily metabolized in the liver to reduced metabolites such as tetrahydrocortisone, followed by glucuronidation and renal excretion. The log Kow value is approximately 1.61, indicating low bioaccumulation potential.

Interactions
Hydrocortisone (80 mg/kg body weight, intraperitoneal injection, for 4 consecutive days), whether used alone or in combination with acetylsalicylic acid (160 mg/kg body weight, oral, for 4 consecutive days), reduces the systemic and specific toxicity of acetylsalicylic acid by modulating the metabolism of drug-metabolizing enzyme systems (intestinal acetylsalicylate esterase and hepatic UDP-glucuronyltransferase), without altering the analgesic effect of acetylsalicylic acid. The effect of glucocorticoids on oral anticoagulation therapy varies from person to person. There are reports that concomitant administration of glucocorticoids may enhance or weaken the efficacy of oral anticoagulants. Patients receiving both glucocorticoids and oral anticoagulants should be monitored (e.g., using coagulation indicators) to maintain the desired anticoagulant effect. /Glucocorticoids/ Estrogen may enhance the effect of hydrocortisone, possibly by increasing the concentration of cortisol transporters, thereby reducing the amount of hydrocortisone available for metabolism.
Potassium-depleting diuretics (e.g., thiazide diuretics, furosemide, ethacrynic acid) and other potassium-depleting drugs (e.g., amphotericin B) may enhance the potassium-depleting effect of glucocorticoids. Patients receiving glucocorticoids and potassium-depleting drugs should have their serum potassium levels closely monitored. /Glucocorticoids/
For more complete data on interactions with hydrocortisone (7 types), please visit the HSDB record page.

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The toxicity of hydrocortisone is closely related to the dosage and duration of administration[s]. Long-term, high-dose use can lead to iatrogenic hyperadrenocorticism (Cushing's syndrome), characterized by moon face, central obesity, skin striae, and easy bruising. Metabolic adverse effects include hyperglycemia, glycosuria, fluid retention, and hypokalemic alkalosis. Musculoskeletal system effects include osteoporosis, pathological fractures, steroid myopathy, and tendon rupture. Gastrointestinal adverse effects include peptic ulcer disease with potential perforation and hemorrhage. Central nervous system effects include euphoria, insomnia, emotional lability, and pseudotumor cerebri. Ophthalmic adverse effects include posterior subcapsular cataracts and glaucoma. Long-term use in children can inhibit growth and development. Gradual tapering is essential upon discontinuation to avoid iatrogenic adrenal insufficiency. Regarding environmental toxicity, the fish plasma model predicts a low environmental risk.

[1]. Differential effects of hydrocortisone and TNFalpha on tight junction proteins in an in vitro model of the human blood-brain barrier. J Physiol. 2008 Apr 1;586(7):1937-49.

[2]. Inhibition of human allergic T-cell responses by IL-10-treated dendritic cells: differences from hydrocortisone-treated dendritic cells. J Allergy Clin Immunol. 2001 Aug;108(2):242-9.

[3]. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology. 2007 Nov;107(5):776-84.

Therapeutic Uses
Anti-inflammatory drugs, steroids. Veterinary drugs: Acute urticaria can be treated with fast-acting corticosteroids, such as hydrocortisone… Veterinary drugs: Intravenous injection, used for the prevention or treatment of adrenal insufficiency and shock-like symptoms, acute allergic reactions, etc., in surgical cases with a history of corticosteroid use, and in cases with high surgical risk and a history of severe systemic infection… Applicable to dogs or cattle… Veterinary drug instructions: Peripheral sensitivity was examined using 5 standard horses and 4 Dutch Warmblood horses. Tissue sensitivity to exogenous insulin was assessed 24 hours after a single injection of hydrocortisone (0.06 mg/kg), eGH (20 μg/kg), or saline (0.9% NaCl), and after long-term (11 to 15 days) eGH injections. Metabolic glucose (M) and plasma insulin concentration (I) were measured. 24 hours after a single injection of hydrocortisone, the M value and M/I ratio were significantly higher than after a single injection of eGH or saline. Following prolonged eGH injections, basal insulin concentrations increased, with the mean M/I ratio decreasing by 22% compared to the saline group. The increase in M value and M/I ratio after a single hydrocortisone injection suggests that short-term hydrocortisone treatment can improve peripheral tissue glucose utilization and insulin sensitivity. Assuming that a single hydrocortisone injection can improve peripheral tissue insulin sensitivity, it may be an effective candidate drug for reducing peripheral tissue insulin resistance in horses with various diseases. For more complete data on the therapeutic uses of hydrocortisone (of 23), please visit the HSDB record page.

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Drug Warning
It is currently unknown whether rectal-administered corticosteroids are excreted into breast milk. Systemically administered corticosteroids are excreted into breast milk and may have adverse effects on infants, such as growth inhibition. Rectal-administered corticosteroids are not recommended for breastfeeding women. /Corticosteroids, Rectal Administration/
Results of a prospective randomized controlled trial investigating the incidence of postoperative diabetes insipidus after three different hydrocortisone regimens, and results of a study investigating the incidence of diabetes insipidus and cortisol response in patients not treated with hydrocortisone, have been published/reported. In Study 1, 114 patients with pituitary macroadenomas were randomized to three groups: the standard dose group (100 mg hydrocortisone intravenously every 6 hours for 3 days); the intermediate dose group (100 mg hydrocortisone intravenously every 6 hours on day 1; 100 mg intravenously every 8 hours on day 2; 100 mg intravenously every 12 hours on day 3); and the low dose regimen (25 mg hydrocortisone intravenously every 6 hours on day 1, 25 mg intravenously every 8 hours on day 2, and 25 mg intravenously every 12 hours on day 3). Radical resection was successfully performed in 92 patients. The incidence of diabetes insipidus was 52% in the standard dose group, 36% in the medium dose group, and 24% in the low dose group (p = 0.025). Study 2 included 16 consecutive patients with Hardy grade A and B pituitary adenomas. These patients were randomly assigned to two groups: receiving (Group I) hydrocortisone treatment and not receiving (Group II) hydrocortisone treatment. Patients in Group II had normal cortisol response during surgery, and no patients developed symptoms of hypocortisolemia; the incidence of diabetes insipidus in this group was 14%. Compared with the standard dose hydrocortisone regimen, the low dose hydrocortisone regimen reduced the incidence of diabetes insipidus by 46%. Perioperative hydrocortisone use can be avoided in patients with grade A and B tumors who have normal preoperative cortisol levels. Acute adrenal insufficiency is caused by premature discontinuation of corticosteroid therapy. /Corticosteroids/ Potential adverse effects on the fetus: Cleft palate, spontaneous abortion, and intrauterine growth retardation have been observed in animal studies. In humans, corticosteroids may cause cleft palate and adrenal suppression, but their teratogenic effects have not been confirmed. Potential side effects in breastfed infants: Small amounts of corticosteroids may pass into breast milk. Physiological doses are unlikely to have adverse effects on infants. FDA Classification: C (C = Laboratory animal studies have shown adverse effects on the fetus (teratogenicity, embryonic lethality, etc.), but there are no controlled studies in pregnant women. Despite the potential risks, the benefits of using this drug in pregnant women may be acceptable, or there are no adequate laboratory animal studies or studies in pregnant women.) /Adrenocortical Hormones/ /Excerpt from Table II/
For more complete data on drug warnings for hydrocortisone (31 of 31), please visit the HSDB record page.

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Pharmacodynamics
Hydrocortisone binds to glucocorticoid receptors, thereby producing downstream effects such as inhibition of phospholipase A2, NF-κB, and other inflammatory transcription factors, as well as promoting the expression of anti-inflammatory genes. Hydrocortisone has a broad therapeutic index and a moderate duration of action. If irritation or allergic reactions occur, the patient should discontinue use of this medication. Cortisol is a 17α-hydroxy-C21-steroid compound with the structure pregn-4-ene, substituted with carbonyl groups at positions 3 and 20, and substituted with hydroxyl groups at positions 11, 17, and 21. Cortisol is a corticosteroid hormone or glucocorticoid secreted by the zona fasciculata (part of the adrenal gland). It is often referred to as a "stress hormone" because it is involved in responses to stress and anxiety and is regulated by corticotropin-releasing hormone (CRH). Cortisol can raise blood pressure and blood sugar and lower immune responses. It has multiple functions, including anti-inflammatory, anti-allergic, anti-asthmatic, human metabolic, mouse metabolic, and drug allergen effects. It is a 21-hydroxysteroid, 11β-hydroxysteroid, 20-oxosteroid, 3-oxo-Δ⁴steroid, primary α-hydroxy ketone, tertiary α-hydroxy ketone, 17α-hydroxy-C21-steroid, and glucocorticoid. It is derived from the hydrogenation of pregnane. Hydrocortisone, or cortisol, is a glucocorticoid secreted by the adrenal cortex. Hydrocortisone is used to treat immune diseases, inflammatory diseases, and neoplastic diseases. It was discovered in the 1930s by Edward Kendall and named compound F or 17-hydroxycorticosterone. Hydrocortisone was approved by the U.S. Food and Drug Administration (FDA) on August 5, 1952. Hydrocortisone is a corticosteroid. The mechanism of action of hydrocortisone is as a corticosteroid hormone receptor agonist. Hydrocortisone has been reported in Ganoderma lucidum, humans, and Rhamnus verticillata, and related data have been published. LOTUS—Natural Products Database. Therapeutic hydrocortisone is a synthetic or semi-synthetic analogue of the natural hydrocortisone hormone produced by the adrenal glands, primarily acting as a glucocorticoid and secondarily as a mineralocorticoid. As a glucocorticoid receptor agonist, hydrocortisone promotes protein catabolism, gluconeogenesis, capillary wall stability, and renal calcium excretion, and inhibits immune and inflammatory responses. (NCI04)
Hydrocortisone is a small molecule drug, with its highest clinical trial stage being Phase IV (covering all indications). It was first approved in 1952 and currently has 35 approved indications and 62 investigational indications. It is the main glucocorticoid secreted by the adrenal cortex. Its synthetic analogues can be administered by injection or topical application to treat inflammation, allergies, collagen diseases, asthma, adrenal insufficiency, shock, and certain neoplastic diseases.

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- Hydrocortisone can stabilize the function of the blood-brain barrier at the molecular level by regulating the expression of tight junction proteins, which is of great significance for maintaining the homeostasis of the central nervous system microenvironment[1]
- It can affect the auxiliary function of dendritic cells (DCs), thereby affecting T cell responses, and has a certain regulatory effect on allergic reactions, which provides a theoretical basis for the treatment of allergic diseases[2]
- Protecting the endothelial glycocalyx is an important mechanism for hydrocortisone to maintain the vascular barrier, which helps prevent interstitial edema and treat related diseases caused by vascular barrier damage[3]

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Hydrocortisone (cortisol) is the main endogenous glucocorticoid. As a potent agonist of glucocorticoid receptor (GR), it can regulate gene expression. Expression [1][2][3]
- Its core mechanisms include upregulating tight junction proteins to maintain the integrity of the epithelial/endothelial barrier, inhibiting dendritic cell maturation to suppress T cell-mediated hypersensitivity, and protecting endothelial glycocalyx from inflammatory/degradative stimulation [1][2][3]
- Clinical applications include anti-inflammatory therapy, immunosuppression, and treatment of diseases involving barrier dysfunction (e.g., vascular leakage caused by sepsis) [1][3]
- In vitro experiments have shown that it has a dose-dependent effect, with physiological concentrations (10-100 nM) modulating immune responses and supraphysiological concentrations (1-10 μM) enhancing barrier function [1][2]
- Unlike IL-10-treated dendritic cells (which induce regulatory T cells), hydrocortisone-treated dendritic cells directly inhibit T cell proliferation and the production of pro-inflammatory cytokines, representing a unique immunomodulatory pathway [2]

C21H30O5

362.46

362.209

C, 69.59; H, 8.34; O, 22.07

50-23-7

Hydrocortisone 17-butyrate;13609-67-1;Hydrocortisone acetate;50-03-3;Hydrocortisone 17-valerate;57524-89-7;Hydrocortisone hemisuccinate;2203-97-6;Hydrocortisone-d7;Hydrocortisone-d4;73565-87-4;Hydrocortisone-d3;115699-92-8;Hydrocortisone phosphate;3863-59-0;Hydrocortisone (Standard);50-23-7;Hydrocortisone-d2;1257650-73-9

5754

White to off-white solid powder

1.3±0.1 g/cm3

566.5±50.0 °C at 760 mmHg

211-214 °C(lit.)

310.4±26.6 °C

0.0±3.5 mmHg at 25°C

1.595

1.43

3

5

2

26

684

7

C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@]4(C(=O)CO)O)C)O

JYGXADMDTFJGBT-VWUMJDOOSA-N

InChI=1S/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1

(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.90 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.90 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2.08 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 5: ≥ 2.08 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)