Glucocorticoid receptor

Resistance or sensitivity to glucocorticoids is considered to be of crucial importance for disease prognosis in childhood acute lymphoblastic leukemia. Prednisolone exerted a delayed biphasic effect on the resistant CCRF-CEM leukemic cell line, necrotic at low doses and apoptotic at higher doses. At low doses, prednisolone exerted a pre-dominant mitogenic effect despite its induction on total cell death, while at higher doses, prednisolone's mitogenic and cell death effects were counterbalanced. Early gene microarray analysis revealed notable differences in 40 genes. The mitogenic/biphasic effects of prednisolone are of clinical importance in the case of resistant leukemic cells. This approach might lead to the identification of gene candidates for future molecular drug targets in combination therapy with glucocorticoids, along with early markers for glucocorticoid resistance [1].

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Prednisolone (0.002-10 μg/mL; 3 days) suppresses human leukocyte mitosis.[5]

Nitric oxide is believed to participate in nonspecific cellular immunity. Gram negative bacterial endotoxins increase the production of reactive nitrogen intermediates (RNI) in phagocytic cells by inducing the enzyme nitric oxide synthase II (NOS II). Anti-inflammatory glucocorticoids attenuate endotoxin-induced increases in RNI. This study evaluated the effect of in vivo administration of prednisolone on Escherichia coli lipopolysaccharide endotoxin (LPS)-induced increases in plasma RNI and neutrophil mRNA for NOS II and production of RNI in the rat. We show that LPS rapidly induces mRNA for NOS II and production of RNI (NO2- and NO3- anion) in rat neutrophils within 2 hr after in vivo administration of a sublethal dose of 0.5 mg/kg, i.v. A pharmacologic dose of prednisolone (50 micrograms/kg, im) given 15 min before LPS-attenuated production of NO2- and NO3- by neutrophils and suppressed LPS-stimulated mRNA for NOS II. 3-Amino, 1,2,4-triazine inhibited NO2- and NO3- production without affecting gene expression for NOS II. These data demonstrate that LPS rapidly induces functional gene expression for NOS II and prednisolone prevents induction of NOS II activity by inhibiting transcription of its mRNA [2].

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Diaphragm atrophy and weakness occur after administration of massive doses of corticosteroids for short periods. In the present study the effects of prolonged administration of moderate doses of fluorinated and nonfluorinated steroids were investigated on contractile properties and histopathology of rat diaphragm. 60 rats received saline, 1.0 mg/kg triamcinolone, or 1.25 or 5 mg/kg i.m. prednisolone daily for 4 wk. Respiratory and peripheral muscle mass increased similarly in control and both prednisolone groups, whereas triamcinolone caused severe muscle wasting. Maximal tetanic tension averaged 2.23 +/- 0.54 kg/cm2 (SD) in the control group. An increased number of diaphragmatic bundles in the 5-mg/kg prednisolone group generated maximal tetanic tensions < 2.0 kg/cm2 (P < 0.05). In addition, fatigability during the force-frequency protocol was most pronounced in this group (P < 0.05). In contrast, triamcinolone caused a prolonged half-relaxation time and a leftward shift of the force-frequency curve (P < 0.05). Histological examination of the diaphragm showed a normal pattern in the control and 1.25-mg/kg prednisolone group. Myogenic changes, however, were found in the 5-mg/kg prednisolone group and, more pronounced, in the triamcinolone group. Selective type IIb fiber atrophy was found in the latter group, but not in the prednisolone groups. In conclusion, triamcinolone induced type IIb fiber atrophy, resulting in reduced respiratory muscle strength and a leftward shift of the force-frequency curve. In contrast, 5 mg/kg prednisolone caused alterations in diaphragmatic contractile properties and histological changes without fiber atrophy [3].

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Since NZB/NZW mice develop an immune nephritis similar to that of systemic lupus erythematosus in man, a study was designed in these mice to compare the clinical and immunologic effects of three immunosuppressive drug regimens. For 72 weeks, groups of 20 mice received daily oral therapy with a) no drugs, b) azathioprine, c) prednisolone or d) combined azathioprine-prednisolone. The combined regimen was superior to either drug used alone in preventing deaths from renal disease. Prednisolone alone also prolonged life significantly, but not as effectively as combination therapy. Azathioprine alone was not effective. All drugs suppressed the antibody response to an exogenous antigen (Vi polysaccharide) equally well. None of the drug regimens prevented the appearance of proteinuria, antinuclear antibodies, Coombs' antibody, or γ-globulin deposits in glomeruli. However, the ability of a therapeutic regimen to suppress antibodies to native DNA correlated well with its ability to suppress renal disease. No malignancies were found among 73 animals autopsied, but significant hepatic damage occurred in the groups receiving prednisolone. Thus, combined therapy was superior to either drug used alone, and the immunosuppressive effect of greatest clinical importance seemed to be the ability to prevent formation of anti-DNA antibodies.[4]

Prednisolone treatment [1]
Concentrations of Prednisolone were selected on the basis of the average in vivo dosage administrated intravenously to children at ages between 1 month and 12 years old (details in supplementary data, file: CCRFCEM Cytotoxixity Assay.xls). Also, bioactivity in cortisol equivalents is estimated to be in the range of 40–200 nM. To ensure that the study covers these ranges, prednisolone was diluted to the following 12 concentrations: control, 10 nM, 100 nM, 1 μM, 5.5 μM, 11 μM, 22 μM, 44 μM, 88 μM, 175 μM, 350 μM, and 700 μM.

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Cell proliferation assay Cell population counts were determined with the use of a NIHON KOHDEN CellTaq-α hematology analyzer. Cells were counted at the −24 h time point as well as 0 h, 4 h, 24 h, 48 h, and 72 h after initiation of exposure to prednisolone. For this purpose, 200 μl of cell suspensions were obtained from each flask and counted directly with the analyzer.

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Protein extraction and Western blotting [1]
Cells were harvested after 1 h and 4 h exposure to different concentrations of Prednisolone. Protein extraction and Western blotting were performed as previously described. Total protein content was determined by the Bradford method using bovine serum albumin as a standard. Proteins were separated by SDS-PAGE and Western blotting was carried out, with anti-p65 antibodies

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Microarray analysis [1]
cDNA microarray chips (1200 genes) were obtained from TAKARA (Human Cancer Chip v.40). Hybridization was performed with the CyScribe Post-Labeling kit as described by the manufacturer, utilizing the Cy3 and Cy5 fluorescent dyes. Slides were scanned with a microarray scanner. Images were generated with ScanArray microarray acquisition software. cDNAs from three experimental setups were used, each one consisting of three independent experiments. The experimental setups consisted of the three following pairs: control vs. 10 nM Prednisolone (designated as 0vs1), 10 nM prednisolone vs. 700 μM prednisolone (designated as 1vs3), control vs. 700 μM prednisolone (designated as 0vs3). This is a ‘simple loop’ experimental design, taking into account all possible combinations between samples, as previously described. Raw microarray data are available as supplementary data.

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Real-time reverse transcription PCR (qRT-PCR) [1]
The GRIM19 (NDUFA13) gene was tested from three samples control, 10 nM and 700 μM Prednisolone at 4 h and 48 h treatment, using the one-step Plexor™ qRT-PCR kit. The set of primers was designed using the on-line tool Plexor™ Primer Design System v1.2 by Promega

Study design, animals, and treatment [3]
60 adult male Wistar rats, aged 14 wk, weighing 350-400 g, were randomized in quadruplets, into one of four treatment groups: control (C), saline, 0.05 ml/d i.m.; low dose prednisolone (LD), 1.25 mg/kg per d i.m.; high dose prednisolone (HD), 5 mg/kg per d i.m.; or triamcinolone-diacetate (TR), 1 mg/kg per d i.m. Dilution of medication was performed such that with each injection all animals received a similar volume (0.05 ml). During 4 wk the animals were injected daily in the left hindlimb. They were fed ad libitum and weighed twice weekly. After the treatment period, contractile properties, histological, and histochemical characteristics of the diaphragm were examined.[3]

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Animal/Disease Models: NZB/NZW mice, immune nephritis model[4]
Doses: 5 mg/ kg/day
Route of Administration: po (oral gavage) 6 days a week for 72 weeks
Experimental Results: Dramatically lowered mortality rate and prolonged life Dramatically.

Absorption, Distribution and Excretion
The Cmax of oral prednisolone is 113-1343 ng/mL, and the Tmax is 1.0-2.6 hours. The bioavailability of oral prednisolone is approximately 70%. More than 98% of prednisolone is excreted in the urine. The volume of distribution (VOD) of prednisolone at a dose of 0.15 mg/kg is 29.3 L, while that at a dose of 0.30 mg/kg is 44.2 L. The clearance of prednisolone at a dose of 0.15 mg/kg is 0.09 L/kg/h, while that at a dose of 0.30 mg/kg is 0.12 L/kg/h. A randomized crossover study compared the pharmacokinetics and pharmacodynamics of 30 mg prednisolone in 8 patients with chronic obstructive pulmonary disease (COPD) (aged 63-81 years) and 8 healthy men after administration of conventionally oral prednisolone tablets (Precortisyl) and enteric-coated tablets (Deltacortril). (Ages 22-44 years). Although the absorption rate of enteric-coated tablets was significantly slower, the peak plasma concentrations and areas under the concentration-time curves were comparable between the two formulations. Adrenal suppression was significantly lower in volunteers taking enteric-coated tablets compared to those taking regular tablets. This difference was not observed in patients. Plasma cortisol levels decreased more slowly in both groups after taking enteric-coated tablets. Blood glucose levels rose within 8 hours in both groups. The conclusion is that, for patients with chronic obstructive pulmonary disease (COPD), the peak plasma concentrations and areas under the concentration-time curves of prednisolone in regular and enteric-coated tablets are comparable. Enteric-coated tablets result in a delayed decrease in plasma cortisol levels, and the cortisol-suppressive effect is weaker in volunteers.
This study investigated the transfer of prednisolone to breast milk in three lactating women (aged 28-37 years) who received 50 mg of prednisolone sodium phosphate (Hydeltrasol) intravenously. The concentration of prednisolone in breast milk decreased faster than in serum, but was similar to the expected concentration in free serum. The concentration of prednisolone in breast milk is approximately 15% to 40% of its serum concentration. The exchange of free drug between serum and breast milk appears to be relatively rapid and bidirectional. On average, 0.025% (0.01–0.49%) of the prednisolone dose is recovered in breast milk. The study concludes that the transfer of prednisolone to breast milk does not appear to pose a clinically significant risk. The pharmacokinetics of prednisolone after oral and intravenous administration of 10 mg and 20 mg were investigated. Serum protein binding of prednisolone was also determined after intravenous administration. The bioavailability was 84.5% after oral administration of 10 mg and 77.6% after 20 mg (p>0.05). The pharmacokinetics of prednisolone were found to be dose-dependent, with significantly higher steady-state volume of distribution (VDss) and clearance (Clt) after intravenous administration of 20 mg compared to 10 mg (p<0.01). The protein binding rate of prednisolone in all subjects was nonlinear, which is likely the main reason for its dose-dependent pharmacokinetic characteristics, as no dose-dependent change was observed in the elimination half-life. Healthy volunteers were administered 16, 32, 48, and 64 mg of prednisolone intravenously, followed by oral administration of 100 mg. Plasma prednisolone concentrations were determined using quantitative thin-layer chromatography. Bioavailability was 1.063 ± 0.154 (standard deviation), indicating complete absorption of prednisolone after oral administration. The mean half-life for all dose groups was 4.11 ± 0.97 (standard deviation) hours, and no dose-related variation was found. The mean systemic clearance for all dose groups was 0.104 ± 0.034 (standard deviation) L/h/kg. No dose-related changes were observed in clearance or apparent volume of distribution (overall mean 0.588 ± 0.152 L/kg). The area under the plasma concentration-time curve was linearly related to the dose. The dose-normalized plasma concentration-time curves were perfectly superimposed. The conclusion is that no nonlinear pharmacokinetic behavior was observed in this group of healthy volunteers within the studied dose range. For more complete data on the absorption, distribution, and excretion of prednisolone (13 in total), please visit the HSDB record page. Metabolites/Metabolites Prednisolone is reversibly metabolized to prednisone, which is then further metabolized to 17α,21-dihydroxypregnane-1,4,6-trien-3,11,30-trione (M-XVII), 20α-dihydroprednisone (MV), 6β-hydroxyprednisone (M-XII), 6α-hydroxyprednisone (M-XIII), or 20β-dihydroprednisone (M-IV). 20β-Dihydroprednisolone is metabolized to 17α,20ξ,21-trihydroxy-5ξ-pregnane-1-en-3,11-dione (M-XVIII). Prednisolone is metabolized to Δ6-prednisolone (M-XI), 20α-dihydroprednisolone (M-III), 20β-dihydroprednisolone (M-II), 6α-hydroxyprednisolone (M-VII), or 6β-hydroxyprednisolone (M-VI). 6α-hydroxyprednisolone is metabolized to 6α,11β,17α,20β,21-pentahydroxypregnane-1,4-dien-3-one (MX). 6β-Hydroxyprednisolone is metabolized to 6β,11β,17α,20β,21-pentahydroxypregnane-1,4-dien-3-one (M-VIII), 6β,11β,17α,20α,21-pentahydroxypregnane-1,4-dien-3-one (M-IX), and 6β,11β,17α,21-tetrahydroxy-5ξ-pregnane-1-en-3,20-dione (M-XIV). MVIII is metabolized to 6β,11β,17α,20β,21-pentahydroxy-5ξ-pregnane-1-en-3-one (M-XV), and then further metabolized to MXIV; while MIX is metabolized to 6β,11β,17α,20α,21-pentahydroxy-5ξ-pregnane-1-en-3-one (M-XVI), and then further metabolized to MXIV. These metabolites and their glucuronide conjugates are primarily excreted in the urine. Reduction of the 4,5 double bond can occur in the liver and extrahepatic sites, producing inactive substances. The reduction of the 3-keto substituent to a 3-hydroxyl group to generate tetrahydrocortisol was only confirmed in the liver. Most α-ring reduction metabolites are enzymatically coupled via a 3-hydroxyl group to sulfate or glucuronidate to form water-soluble sulfate esters or glucuronides, which are then excreted in these forms.
They are primarily bound in the liver, but also in the kidneys. /Human, Oral/
This study re-examined the metabolism of prednisolone in ex vivo perfused dual-circulation human placental lobules using a perfusion medium based on tissue culture medium 199. Four metabolites were identified in both the maternal and fetal compartments during a 6-hour perfusion by comparing the relative retention times determined by high-performance liquid chromatography (HPLC) and capillary gas chromatography (GC), as well as the relative retention times of mass spectra recorded by capillary GC/MS with those of standards. These steroids were derivatized into MO-TMS ethers for mass spectrometry measurements. Analysis of samples from five perfusion experiments showed that, 6 hours after perfusion, the conversion rates of maternal and fetal perfusion fluids were as follows (mean ± standard deviation): prednisone (49.1 ± 7.8, 49.1 ± 6.6), 20α-dihydroprednisone (0.84 ± 0.29, 0.81 ± 0.35), 20β-dihydroprednisone (39.1 ± 6.7, 39.2 ± 5.9), 20β-dihydroprednisolone (6.8 ± 2.7, 6.3 ± 1.6), and unmetabolized prednisolone (4.1 ± 1.8, 4.6 ± 2.1). No evidence of metabolites formed by 6β-hydroxylation or C17-C20 bond cleavage was found. A randomized, four-period crossover study was conducted in eight healthy male volunteers to determine the relative and absolute bioavailability of prednisone (PN) and prednisolone (PL). PN and PL were administered via a single oral 10 mg tablet and a 10 mg zero-order 0.5-hour intravenous infusion, respectively. The mean maximum plasma concentration (Cmax), time to peak concentration, area under the plasma concentration-time curve (AUC), and apparent elimination rate constant were comparable between the tablet treatment groups, indicating bioequivalence between the PN and PL tablets. Absolute bioavailability (F) measurements based on plasma PL concentrations were independent of the intravenous infusion method used as a reference, indicating that PL in both PN and PL tablets is completely systemically utilized. However, F values based on plasma PN data were contradictory. With intravenous PN as a reference, the systemic bioavailability of both tablets was approximately 70%; while with intravenous PL as a reference, the systemic bioavailability was greater than 1. PN and PL are model compounds, highlighting the difficulty in accurately determining the relative and absolute bioavailability of reversible metabolites. Currently, prednisone, prednisolone, and methylprednisolone are used in combination with cyclosporine A for post-transplant treatment. This study aimed to evaluate the effects of these corticosteroids on the expression of various cytochrome P450s (including P450 1A2, 2D6, 2E1, and 3A) and cyclosporine A oxidase activity in human liver. For this purpose, human hepatocytes obtained from hepatectomy were cultured in serum-free medium in collagen-coated dishes for 96–144 hours, with or without 50–100 μM corticosteroids, rifampin, or dexamethasone. To more closely resemble current clinical protocols, hepatocyte cultures were also treated with corticosteroids and either cyclosporine A or ketoconazole (a selective cytochrome P450 3A inhibitor). In these cultures, the activity of cyclosporine A oxidase, the retention of cyclosporine A oxidative metabolites in hepatocytes, the accumulation of cytochrome P450 protein and its corresponding mRNA, and the de novo synthesis and half-life of these cytochrome P450s were measured in parallel. Our results from seven different hepatocyte cultures indicate that: 1) Dexamethasone and prednisone (but not prednisolone or methylprednisolone) are inducers of cytochrome P450 3A, inducing its expression at both protein and mRNA accumulation levels, and also inducing cyclosporine A oxidase activity (known to be primarily catalyzed by these cytochrome P450s); 2) Although corticosteroids are known to be metabolized in the human liver, particularly through cytochrome P450 3A, partial or complete inhibition of this cytochrome P450 by cyclosporine or ketoconazole does not affect the induction efficiency of these molecules; 3) Corticosteroids do not affect the half-life of cytochrome P450 3A or the accumulation of other forms of cytochrome P450 (including 1A2, 2D6, and 2E1); 4) Long-term cyclosporine treatment of cells does not affect the accumulation of cytochrome P450 3A; 5) All corticosteroids are competitive inhibitors of cyclosporine A oxidase in human liver microsomes. The Ki values of dexamethasone, prednisolone, prednisolone, and methylprednisolone were 61±12 μM, 125±25 μM, 190±38 μM, and 210±42 μM, respectively; 6) Long-term treatment of cells with corticosteroids does not affect the excretion of cyclosporine oxidative metabolites in cells.

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Biological half-life
The plasma half-life of prednisolone is 2.1-3.5 hours. The half-life is shorter in children and longer in patients with liver disease.
...Twenty-three children with acute lymphoblastic leukemia (ALL) (aged 2-15 years) were given prednisolone orally and intravenously (60 mg/m²/day, divided into three doses), and samples were collected multiple times during the first 5 weeks of remission induction therapy. ...The median free clearance (32 L/hr/m²) was lower than previously reported in pediatric ALL, while the half-life (3.6 hours) was longer than previously reported. Healthy volunteers received intravenous injections of 16, 32, 48, and 64 mg prednisolone, respectively, concurrently with oral administration of 100 mg prednisolone. ...The mean half-life across all dose groups was 4.11 ± 0.97 (standard deviation) hours, and no dose-related changes in half-life were observed.

Interactions
Seizures have been observed in patients receiving cyclosporine and high-dose methylprednisolone. /Methylprednisolone
In one study, women taking oral contraceptives or receiving postmenopausal estrogen therapy concurrently received prednisolone. Alterations in prednisolone metabolism, including a prolonged half-life, are consistent with the potential for enhanced pharmacological effects or toxicity when prednisolone is added to estrogen therapy regimens.
Ketoconazole inhibits prednisolone deposition by inhibiting 6β-hydroxylase, thereby prolonging the adrenal inhibitory effect of prednisolone.
Drugs that can increase cyclosporine blood concentrations include prednisolone.
For more complete data on prednisolone interactions (out of 26), please visit the HSDB record page.

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Non-human toxicity values
Mouse intraperitoneal LD50 > 1000 mg/kg body weight (prednisolone acetate)
Mouse intraperitoneal LD50 767 mg/kg body weight
Swiss mouse oral LD50 1680 mg/kg body weight
Sherman rat (male) subcutaneous injection 147 mg/kg body weight

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Effects during pregnancy and lactation
◉ Overview of use during lactation
Prednisolone is present in extremely low concentrations in breast milk. No adverse effects have been reported on breastfed infants from the use of any corticosteroid by lactating mothers. While it is generally recommended to avoid breastfeeding for 4 hours after administration, this is unnecessary due to the extremely low concentrations of prednisolone in breast milk. Moderate to high doses of corticosteroids administered systemically or injected into the joints or breast have been reported to cause a temporary decrease in lactation.
Due to limited absorption through the eyes, ophthalmic prednisolone is not expected to have any adverse effects on breastfed infants. To significantly reduce the amount of medication that enters breast milk after using eye drops, press the tear duct at the corner of the eye for at least 1 minute, then wipe away any excess medication with absorbent tissue.
◉ Effects on Breastfed Infants
No effects have been reported on breastfed infants from the use of prednisolone or any other corticosteroid. In a prospective follow-up study, 6 breastfeeding mothers reported no adverse effects on their infants from prednisone use (dosage not specified). Several case reports have shown no adverse effects on infants from mothers who breastfed during prolonged corticosteroid use: 10 mg prednisone daily (2 infants) and 5 to 7.5 mg prednisolone daily (14 infants).
A mother who was breastfeeding (breastfeeding duration not specified) received oral prednisolone for pemphigus, starting at 25 mg daily and increasing to 60 mg daily over two weeks. She also received cetirizine 10 mg/day and applied 0.1% betamethasone ointment to the lesions twice daily. Due to poor efficacy, the betamethasone ointment was changed to 0.05% clobetasol propionate ointment. She continued breastfeeding throughout the treatment, and the infant developed normally at 8 weeks of age and beyond.
A woman with gestational pemphigoid received prednisolone while breastfeeding, with the dose gradually reduced from 0.7 mg/kg daily to 1 mg daily. She also received intravenous immunoglobulin for three days at 3 weeks postpartum, at a dose of 2 g/kg. She breastfed her infant for three months (breastfeeding duration not specified) without any problems. Two mothers with systemic lupus erythematosus reportedly took prednisolone 30 or 40 mg daily and tacrolimus 3 mg daily during pregnancy and lactation. Both children were healthy three years after birth. The lactation period was not specified. A patient with rheumatoid arthritis unresponsive to etanercept took 200 mg of thalidomide every two weeks during pregnancy until week 37. She also took prednisolone 10 mg and tacrolimus 3 mg daily. She gave birth to a healthy baby at week 38 and breastfed. She continued taking prednisolone postpartum, restarted tacrolimus 7 days postpartum, and restarted thalidomide 28 days postpartum. The mother continued breastfeeding for six months postpartum. The infant received multiple live vaccines, including BCG, at six months of age without adverse reactions.
◉ Effects on Lactation and Breast Milk
As of the revision date, no published information was found regarding the effects of prednisolone on serum prolactin or lactation in breastfeeding mothers. Systemic administration or intra-articular or breast injection of moderate to high doses of corticosteroids has been reported to cause a temporary reduction in lactation.
A study of 46 women who delivered before 34 weeks of gestation found that administration of another corticosteroid (betamethasone, 11.4 mg intramuscularly twice 24 hours apart) 3 to 9 days before delivery resulted in delayed lactation stage II and a reduction in average milk production within 10 days postpartum. Milk production was unaffected if the infant was delivered within 3 or 10 days of the mother's corticosteroid administration. Equivalent doses of prednisolone may have the same effect. A study of 87 pregnant women found that betamethasone administration during pregnancy as described above resulted in a premature increase in lactose secretion during pregnancy. While this increase was statistically significant, its clinical significance appears negligible. Equivalent doses of prednisolone may have the same effect.

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5755tmantTDLotoralt9 mg/kg/2W-It Behavioral Science: Information on Toxic Psychotropic Drugs and Clinical Pharmacy, 18(603), 1984 [PMID:6745088]
5755twomentTDLotoralt14 mg/kg/13D-It Behavioral Science: Information on Toxic Psychotropic Drugs and Clinical Pharmacy, 18(603), 1984 [PMID:6745088]
5755trattLD50tintraperitonealt2 gm/kgtt Advances in Teratology, 3(181), 1968
5755trattLD50tsubcutaneoust147 mg/kgtt Toxicology and Applied Pharmacology, 8(250), 1966 [PMID:5956877]
5755trattLD50tintravenoust120 mg/kgtt Journal of Medicinal Chemistry, 16(63), 1982

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Protein binding
The protein binding rate of prednisolone varies greatly, ranging from 65-91% in healthy patients.

[1]. Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells: Relation to early gene expression. Leuk Res, 2009. 33(12): p. 1684-95.

[2]. Rapid induction of messenger RNA for nitric oxide synthase II in rat neutrophils in vivo by endotoxin and its suppression by prednisolone. Proc Soc Exp Biol Med. 1994 Mar;205(3):220-9.

[3]. Triamcinolone and prednisolone affect contractile properties and histopathology of rat diaphragm differently. J Clin Invest. 1993 Sep;92(3):1534-42.

[4]. Comparison of therapeutic and immunosuppressive effects of azathioprine, prednisolone and combined therapy in nzp/nzw mice. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, 1973, 16(2): 163-170.

[5]. Inhibition of human leukocyte mitosis by prednisolone in vitro. Cancer Res. 1961 Dec;21:1518-21.

Therapeutic Uses
Anti-inflammatory drugs, steroids; antitumor drugs, hormones; synthetic glucocorticoids. Ophthalmic corticosteroids are indicated for the treatment of allergic and inflammatory diseases of the palpebral conjunctiva, bulbar conjunctiva, cornea, and anterior segment of the eye that are sensitive to corticosteroids. /Corticosteroids (ophthalmic); included in the US product label/ Veterinary: Hormonal therapy for tumors often involves the use of glucocorticoids. Their direct antitumor effect is related to their lympholytic properties; glucocorticoids can inhibit mitosis, RNA synthesis, and protein synthesis in sensitive lymphocytes. Glucocorticoids are considered non-cell cycle specific and are often used in chemotherapy regimens after induction by other drugs. Prednisolone is often used in combination with other drugs to treat lymphoreticular tumors. Due to its easy entry into the cerebrospinal fluid, prednisolone is particularly suitable for the treatment of central nervous system leukemia and lymphoma. Suitable for a variety of endocrine, rheumatic, allergic, skin, respiratory, hematologic, oncological, and other diseases. For more complete data on the therapeutic uses of prednisolone (28 types in total), please visit the HSDB record page.

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Drug Warnings
Veterinarians: This product may generally be contraindicated in patients with congestive heart failure, diabetes, or osteoporosis. Except for emergency life-saving uses, it should be avoided in patients with tuberculosis, chronic nephritis, Cushing's syndrome, and peptic ulcers.
This study assessed side effects and adherence in 63 children (aged 10 months to 14 years) with acute asthma. These children received oral prednisolone (Solone; Panafcortelone) at a dose of 1–2 mg/kg, administered as a whole tablet, crushed tablet, or liquid, for 7 days. Up to 44% of the children refused the medication or vomited on day 1. Tolerance to prednisolone improved over time, but prescribing practice suggests that short-term treatment of 1–4 days is more common. At some point during the study, 19% and 80% of the children, respectively, experienced abdominal pain and mood changes. Research findings indicate that oral prednisolone is poorly tolerated in pediatric patients, and its use may lead to suboptimal efficacy. Children using glucocorticoids not only experience the same side effects as adults but also suffer serious adverse effects on height development. Even daily doses of only 2.5-5.0 mg of prednisolone can cause stunted growth. There is a direct relationship between glucocorticoid dosage and height development. Osteometry is a sensitive technique for measuring long bone growth in children, and its application improves the accuracy of growth rate measurements. When assessing the effects of specific glucocorticoids on height, many factors must be considered, such as disease progression, sex, daily versus every-other-day dosing, racial differences, and whether the patient is bedridden. Controlled trial results indicate that prednisolone treatment is ineffective and may even be harmful in acute neuropathy of unknown etiology. For more complete data on prednisolone (48 total), please visit the HSDB record page.

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Pharmacodynamics
Glucocorticoids bind to glucocorticoid receptors, inhibiting pro-inflammatory signaling and promoting anti-inflammatory signaling.
Prednisolone has a short duration of action, with a half-life of 2.1-3.5 hours. Glucocorticoids have a wide therapeutic window, and patients may need to take several times the dose naturally produced by the body. Patients taking corticosteroids should be informed of the risks of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infection.

C21H28O5

360.44

360.193

C, 69.98; H, 7.83; O, 22.19

50-24-8

Prednisolone;50-24-8; Prednisolone;50-24-8;Prednisolone hemisuccinate;2920-86-7;Prednisolone acetate;52-21-1; 630-67-1 (sodium metazoate); 72064-79-0 (valerate acetate); 125-02-0 (Na+ phosphate)

5755

White to off-white solid powder

1.3±0.1 g/cm3

570.6±50.0 °C at 760 mmHg

240 °C (dec.)(lit.)

313.0±26.6 °C

0.0±3.6 mmHg at 25°C

1.612

1.5

3

5

2

26

724

7

C[C@]12C[C@@H]([C@H]3[C@H]([C@@H]1CC[C@@]2(C(=O)CO)O)CCC4=CC(=O)C=C[C@]34C)O

OIGNJSKKLXVSLS-VWUMJDOOSA-N

InChI=1S/C21H28O5/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/h5,7,9,14-16,18,22,24,26H,3-4,6,8,10-11H2,1-2H3/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-7,8,9,11,12,14,15,16-octahydro-6H-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

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: ≥ 2.08 mg/mL (5.77 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 20.8 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: ≥ 2.08 mg/mL (5.77 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 3: ≥ 2.08 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

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