Prednisolone

Pharmaceuticals -> Steroids

Pharmaceuticals -> Metabolite of Prednisone

Pharmaceuticals -> Listed in ZINC15

log Kow = 1.62

1

Crystals

White to practically white crystalline powder

SPECIFIC OPTICAL ROTATION: +102.5 DEG @ 25 °C/D; PH OF 1% SOLN 7.5 TO 8.5; SOL IN WATER, METHANOL, ETHANOL. /PHOSPHATE SODIUM/

1 g dissolves in about 30 mL of alc, in about 180 mL of chloroform, in about 50 mL of acetone; sol in methanol, dioxane.

In water, 2.23X10+2 mg/L at 25 °C

2.39e-01 g/L

Breast Feeding; Lactation; Milk, Human; Corticosteroids, Systemic; Corticosteroids, Ophthalmic; Glucocorticoids; Anti-Inflammatory Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Anti-inflammatory medicines

EMA approved medicines: Veterinary medicine

Active Ingredients (Prednisolone) -> FDA Greenbook

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Pharmaceuticals -> UK Veterinary Medicines Directorate List

235 °C with some decomposition

CRYSTALS FROM ETHANOL; MP: 266-273 °C /TEBUTATE/

235 °C

This chemical does not meet GHS hazard criteria for 0.5% (1 of 207) of reports.

Danger

H302 (31.9%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P264, P270, P271, P273, P280, P301+P317, P304+P340, P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 207 reports by companies from 29 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Status: Active Update: 04-05-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/14158

Prednisolone: Does not have an individual approval but may be used under an appropriate group standard

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prednisolone approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prednisolone sodium phosphate approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prednisolone sodium phosphate/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prednisolone acetate approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prednisolone acetate/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products, incl prednisolone tebutate. /Prednisolone tebutate/

For more FDA Requirements (Complete) data for PREDNISOLONE (15 total), please visit the HSDB record page.

Ali SL; Prednisolone; Anal Profiles Drug Subst Excipients 21: 415-500 (1992). A review with 153 references on the synthesis, properties, pharmacology, and analysis of prednisolone.

Wald JA et al; Evaluation of Dose-Related Pharmacokinetics and Pharmacodynamics of Prednisolone in Man; J Pharmacokinet Biopharm 20 (Dec): 567-89 (1992). To investigate the pharmacokinetics and pharmacodynamics of prednisolone and to develop predictive models, 7 healthy volunteers, ages 21-37 yr, received between 16.4 and 49.2 mg of iv prednisolone sodium phosphate (Hydeltrasol) on 2 occasions in increasing doses; blood and urine samples were taken frequently and analyzed for pharmacokinetic parameters, suppression of plasma cortisol, and alterations in blood basophil and helper-T cells trafficking. Results indicated that the pharmacokinetics of total drug were comparable to previous findings. Pharmacodynamic models characterized the suppression/trafficking phenomenon with the use of total or free drug concn. It was concluded that the models provided realistic values of parameters relating to steroid sensitivity.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Seizures have been observed in patients receiving cyclosporine and high doses of methylprednisolone. /Methylprednisolone

In one study, women taking oral contraceptives or postmenopausal estrogen therapy were given prednisolone concurrently. Alterations in metabolism of prednisolone, including incr half-life, were consistent with a potential for enhanced pharmacologic effect or toxicity when prednisolone was added to an estrogen regimen.

Ketoconazole inhibits the deposition of ... prednisolone by inhibiting 6beta-hydroxylase, thereby prolonging the adrenal suppressive effect of ... /prednisolone/.

Drugs reported to increase blood levels of cyclosporine include ... prednisolone.

For more Interactions (Complete) data for PREDNISOLONE (26 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 180(SRC), determined from a log Kow of 1.62(2) and a regression-derived equation(3), indicates that prednisolone is expected to have moderate mobility in soil(SRC). Volatilization of prednisolone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.7X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Prednisolone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-13 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data for prednisolone were not available (SRC, 2007).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 180(SRC), determined from a log Kow of 1.62(2) and a regression-derived equation(3), indicates that prednisolone is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.7X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(6), an estimated BCF of 3.5(SRC), from an estimated log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data for prednisolone were not available (SRC, 2007).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), prednisolone, which has an estimated vapor pressure of 1.2X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase prednisolone may be removed from the air by wet or dry deposition(SRC). Prednisolone contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight.

Corticosteroids may be distributed into milk ... . /Corticosteroids/

The transfer of prednisolone to breast milk was studied in 3 nursing women (ages 28-37 yr) who received an intravenous injection of 50 mg prednisolone sodium phosphate (Hydeltrasol). Concn of prednisolone in milk declined more rapidly than in serum, but were similar to expected unbound serum levels. Milk levels ranged from about 15% to 40% of serum levels. The exchange between unbound drug in serum and breast milk appeared to be relatively rapid and bidirectional. An average of 0.025% (0.01-0.49%) of the prednisolone dose was recovered in milk.

/AQUATIC SPECIES/ Light exposure of aqueous suspensions of prednisolone and dexamethasone causes their partial phototransformation. The photoproducts, isolated by chromatographic techniques, have been identified by spectroscopic means. Prednisolone, dexamethasone and their photoproducts have been tested to evaluate their acute and chronic toxic effects on some freshwater chain organisms. The rotifer Brachionus calyciflorus and the crustaceans Thamnocephalus platyurus and Daphnia magna were chosen to perform acute toxicity tests, while the alga Pseudokircheneriella subcapitata (formerly known as Selenastrum capricornutum) and the crustacean Ceriodaphnia dubia to perform chronic tests. The photochemical derivatives are more toxic than the parent compounds. Generally low acute toxicity was found. Chronic exposure to this class of pharmaceuticals caused inhibition of growth population on the freshwater crustacean C. dubia while the alga P. subcapitata seems to be less affected by the presence of these drugs.

The Koc of prednisolone is estimated as 180(SRC), using a log Kow of 1.62(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that prednisolone is expected to have moderate mobility in soil.

/SIGNS AND SYMPTOMS/ Glucocorticoids may cause fetal damage when administered to pregnant women. One retrospective study of 260 women who received pharmacologic dosages of glucocorticoids during pregnancy revealed 2 instances of cleft palate, 8 stillbirths, 1 spontaneous abortion, and 15 premature births. Another study reported 2 cases of cleft palate in 86 births. Occurrence of cleft palate in these studies is higher than in the general population but could have resulted from the underlying diseases as well as from the steroids. Other fetal abnormalities that have been reported following glucocorticoid administration in pregnant women include hydrocephalus and gastroschisis. Women should be instructed to inform their physicians if they become or wish to become pregnant while receiving glucocorticoids. If glucocorticoids must be used during pregnancy or if the patient becomes pregnant while taking one of these drugs, the potential risks should be carefully considered. /Corticosteroids/

/CASE REPORTS/ Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. CASE Two cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type) /are described/. The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests.

/CASE REPORTS/ The case of a 27-year-old female who had an allergic contact dermatitis to topical corticosteroids belonging to the corticosteroid groups A and D /was reported/. Upon oral treatment with prednisolone a disseminated exanthema began within 24 hr. Patch tests revealed sensitization to corticosteroids of group A, C and D, including prednisolone-21-acetate and betamethasone valerate, but not of group B corticosteroids such as triamcinolone. After intradermal testing of corticosteroids the exanthema flared again and the patient was treated with oral triamcinolone, with rapid improvement of her symptoms. A literature review revealed that exanthematous reactions after systemic treatment with corticosteroids have been rarely reported. Since corticosteroids are essential emergency drugs, a safe corticosteroid should be identified for such patients.

/CASE REPORTS/ Although positive reactions to topical corticosteroids can occur in over 1% of a patch-test population, systemic reactions to oral corticosteroids are uncommon. A 45-year-old woman who gave a clear history of the generalization of a cutaneous eruption following oral prednisolone was positive on patch testing using prednisolone eye drops.

For more Human Toxicity Excerpts (Complete) data for PREDNISOLONE (7 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Prednisolone

vLess-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

An estimated BCF of 3.5 was calculated for prednisolone(SRC), using a log Kow of 1.62(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC), provided the compound is not metabolized by the organism(SRC).

The Henry's Law constant for prednisolone is estimated as 2.7X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that prednisolone is expected to be essentially nonvolatile from water surfaces(2). Prednisolone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-13 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Acute Exposure/ Various tests for irritation, phototoxicity, contact sensitivity and photocontact sensitivity of prednisolone farnesylate gel were conducted. The results were as follows. 1) In the primary dermal irritation test and trypan blue test, slight erythema was noted in the rabbits treated with 0.8 and 1.6% prednisolone farnesylate gel, although similar reaction occurred in those treated with the base. 2) In the test for the primary irritation to the ocular mucosa, severe irritant reactions were caused by 0.8 and 1.6% prednisolone farnesylate gel and its base. However these reactions disappeared 7 days after irritation. 3) In the phototoxicity test and contact sensitivity test, no positive reactions were detected by 0.8 and 1.6% prednisolone farnesylate gel. On the other hand, in the photocontact sensitivity test, positive reaction were noted in the guinea pig treated with 0.8 and 1.6% prednisolone farnesylate gel and its base. /Prednisolone farnesylate/

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The toxicity of prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.25, 1, 4 and 16 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 10 mg/kg/day prednisolone gel, which is approximate to 16 mg/kg/day prednisolone farnesylate gel in prednisolone molarity, was also administered to the rats for comparison. The results are summarized as follows: 1. In the prednisolone farnesylate gel 16 mg/kg/day group, temporary erythema at the application site, retarded body weight gains, a decrease in the white blood cell count and lymphocyte ratio with an increase in the segmented neutrophil ratio, an elevation of serum ALP activity were observed. The pathological examinations revealed atrophy of the adrenal glands, lymphatic organs and skin. In addition, histopathological lesions were also found in the liver, pancreatic islets, bone, bone marrow and mammary glands. 2. In the prednisolone farnesylate gel 4 mg/kg/day group, retarded body weight gains were observed, and histopathological lesions were noted in the adrenal glands, lymphatic organs, skin at the application site, liver and bone marrows. 3. In the groups that received less than 1 mg/kg/day of prednisolone farnesylate gel, there were no toxic signs induced by the drug. 4. In the prednisolone gel 10 mg/kg/day group, drug-related changes were almost similar to those of the prednisolone farnesylate gel group, but the severity of the lesions was stronger than in the prednisolone farnesylate gel group. 5. After the 5-week recovery period, the above changes almost completely disappeared and so it was demonstrated that the changes were reversible. 6. Based on these results, it was concluded that the overt toxic dose of prednisolone farnesylate gel was 4 mg/kg/day and the non-toxic dose was 1 mg/kg/day in the present study.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Repeated dose toxicity studies were also carried out in rabbits (intramuscular doses of 0.5 to 2.5 mg prednisolone acetate/kg body weight, for up to 22 doses) and guinea pigs (intramuscular dose of 2.2 mg prednisolone/kg body weight for up to 8 doses and oral doses of 0, 1, or 10 mg prednisolone/kg body weight administered in the drinking water or 0, 10, or 100 mg/kg body weight administered in the feed for 24 weeks). ... Hepatotoxicity was observed at the lowest dose tested in rabbits and ws dose-related in severity; rabbits appeared to be the species most susceptible to this effect. In guinea pigs the main effects were reduced body-weight gain (apparent at the lowest dose of 1 mg/kg body weight), increase in hematocrit and hemoglobin values and decreased bone mineral concentrations.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Groups of Mongrel dogs (2 animals per sex and dose) were given daily oral doses of 0, 2.5 or 5 mg/kg body weight per day for 6 weeks. Bodyweight gain was reduced at 5 mg/kg body weight. There was no significant effects on hematology or clinical chemistry values. There were dose-related increase in urine volume and mean urine sodium and potassium concentrations and a corresponding reduction in urinary specific gravity. At necropsy, glycogen deposition in the liver and adrenal cortical atrophy were found in treated dogs.

For more Non-Human Toxicity Excerpts (Complete) data for PREDNISOLONE (14 total), please visit the HSDB record page.

Glucocorticoids should be used with caution in patients with hypothyroidism or cirrhosis, because such patients often show exaggerated response to the drugs. Glucocorticoids should be used with caution in psychotic patients or patients with hypertension or congestive heart failure. /Corticosteroids/

Because an apparent association has been suggested between use of corticosteroids and left ventricular free-wall rupture after a recent myocardial infarction, corticosteroids should be used with extreme caution in these patients. /Corticosteroids/

Because glucocorticoids increase susceptibility to and mask symptoms of infection, the drugs should not be used, except in life-threatening situations, in patients with viral infections or bacterial infections not controlled by anti-infectives. Manufacturers state that glucocorticoid oral inhalation therapy should be used with caution, if at all, in patients with untreated systemic fungal, bacterial, viral, or parasitic infections. Patients whose susceptibility to infection is high, such as those receiving glucocorticoids as immunosuppressive therapy, are especially likely to develop secondary infections. Patients receiving glucocorticoids who are potentially immunosuppressed should be warned of the risk of exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs. Since glucocorticoid therapy can reactivate tuberculosis, treatment of latent tuberculosis infection should be included in the regimen of patients with a history of active tuberculosis undergoing prolonged glucocorticoid therapy. If glucocorticoids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary. Use of glucocorticoids in patients with active tuberculosis should be restricted to those with fulminating or disseminated tuberculosis in which glucocorticoids are used in conjunction with appropriate antimycobacterial chemotherapy. Manufacturers state that glucocorticoid oral inhalation therapy should be used with caution, if at all, in patients with clinical or asymptomatic Mycobacterium tuberculosis infections of the respiratory tract. Since glucocorticoids can reactivate latent amebiasis, any patient who has been in the tropics or who has unexplained diarrhea should be evaluated for amebiasis to exclude these patients prior to initiating therapy. In the treatment of acute or disseminated tuberculosis, glucocorticoids should only be used as part of a total antituberculosis regimen. ... /Corticosteroids/

Corticosteroids should be used with caution in patients with active or latent peptic ulcer, diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), and in those with recent intestinal anastomoses. Manifestations of peritoneal irritation following GI perforation may be minimal or absent in patients receiving glucocorticoids. /Corticosteroids/

Glucocorticoids may cause fetal damage when administered to pregnant women. One retrospective study of 260 women who received pharmacologic dosages of glucocorticoids during pregnancy revealed 2 instances of cleft palate, 8 stillbirths, 1 spontaneous abortion, and 15 premature births. Another study reported 2 cases of cleft palate in 86 births. Occurrence of cleft palate in these studies is higher than in the general population but could have resulted from the underlying diseases as well as from the steroids. Other fetal abnormalities that have been reported following glucocorticoid administration in pregnant women include hydrocephalus and gastroschisis. Women should be instructed to inform their physicians if they become or wish to become pregnant while receiving glucocorticoids. If glucocorticoids must be used during pregnancy or if the patient becomes pregnant while taking one of these drugs, the potential risks should be carefully considered. /Corticosteroids/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prednisolone approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prednisolone sodium phosphate approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prednisolone sodium phosphate/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prednisolone acetate approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prednisolone acetate/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products, incl prednisolone tebutate. /Prednisolone tebutate/

For more FDA Requirements (Complete) data for PREDNISOLONE (15 total), please visit the HSDB record page.

S01BA04

S - Sensory organs

C - Cardiovascular system

A - Alimentary tract and metabolism

H - Systemic hormonal preparations, excl. sex hormones and insulins

D - Dermatologicals

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisolone has a short duration of action as the half life is 2.1-3.5 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

Although altered homeostatic regulation, including disturbance of 24-h rhythms, is often observed in the patients undergoing glucocorticoid therapy, the mechanisms underlying the disturbance remains poorly understood. We report here that chronic treatment with a synthetic glucocorticoid, prednisolone, can cause alteration of circadian clock function at molecular level. Treatment of cultured hepatic cells (HepG2) with prednisolone induced expression of Period1 (Per1), and the prednisolone treatment also attenuated the serum-induced oscillations in the expression of Period2 (Per2), Rev-erbalpha, and Bmal1 mRNA in HepG2 cells. Because the attenuation of clock gene oscillations was blocked by pretreating the cells with a Per1 antisense phosphothioate oligodeoxynucleotide, the extensive expression of Per1 induced by prednisolone may have resulted in the reduced amplitude of other clock gene oscillations. Continuous administration of prednisolone into mice constitutively increased the Per1 mRNA levels in liver and skeletal muscle, which seems to attenuate the oscillation in the expressions of Per2, Rev-erbalpha, and Bmal1. However, a single daily administration of prednisolone at the time of day corresponding to acrophase of endogenous glucocorticoid levels had little effect on the rhythmic expression of clock genes. These results suggest a possible pharmacological action by prednisolone on the core circadian oscillation mechanism and indicate the possibility that the alteration of clock function induced by prednisolone can be avoided by optimizing the dosing schedule.

Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/

Prednisolone has a plasma half life of 2.1-3.5 hours. This half life is shorter in children and longer in those with liver disease.

...Prednisolone (60 mg/sq m/day in three divided doses) was administered both orally and intravenously /to 23 children with acute lymphoblastic leukemia (ALL) (aged 2-15 years)/, and samples were obtained on several days during the initial 5 weeks of remission induction therapy. ...The median unbound clearance (32 L/hr/sq m) was lower, and the half-life (3.6 hr) longer than previously reported in childhood ALL.

Doses of 16, 32, 48 and 64 mg prednisolone were administered intravenously to normal volunteers who also received 100 prednisolone orally. ...The mean T 1/2 over all doses were 4.11 +/- 0.97 (s.d.) hr and there was no evidence of a dose-related change in its value.

Prednisolone can be reversibly metabolized to [prednisone] which is then metabolized to 17α,21-dihydroxy-pregnan-1,4,6-trien-3,11,30-trione (M-XVII), 20α-dihydro-prednisone (M-V), 6βhydroxy-prednisone (M-XII), 6α-hydroxy-prednisone (M-XIII), or 20β-dihydro-prednisone (M-IV). 20β-dihydro-prednisone is metabolized to 17α,20ξ,21-trihydroxy-5ξ-pregn-1-en-3,11-dione(M-XVIII). Prednisolone is metabolized to Δ6-prednisolone (M-XI), 20α-dihydro-prednisolone (M-III), 20β-dihydro-prednisolone (M-II), 6αhydroxy-prednisolone (M-VII), or 6βhydroxy-prednisolone(M-VI). 6αhydroxy-prednisolone is metabolized to 6α,11β,17α,20β,21-pentahydroxypregnan-1,4-diene-3-one (M-X). 6βhydroxy-prednisolone is metabolized to 6β,11β,17α,20β,21-pentahydroxypregnan-1,4-diene-3-one (M-VIII), 6β,11β,17α,20α,21-pentahydroxypregnan-1,4-diene-3-one (M-IX), and 6β,11β,17α,21-tetrahydroxy-5ξ-pregn-1-en-3,20-dione (M-XIV). MVIII is metabolized to 6β,11β,17α,20β,21-pentahydroxy-5ξ-pregn-1-en-3-one (M-XV) and then to MXIV, while MIX is metabolized to 6β,11β,17α,20α,21-pentahydroxy-5ξ-pregn-1-en-3-one (M-XVI) and then to MXIV. These metabolites and their glucuronide conjugates are excreted predominantly in the urine.

Reduction of the 4,5 double bond can occur at both hepatic and extrahepatic sites and yields an inactive substance. Subsequent reduction of the 3-ketone substituent to a 3-hydroxyl to form tetrahydrocortisol has been demonstrated only in liver. Most of the ring a - reduced metabolites are enzymatically coupled through the 3-hydroxyl with sulfate or with glucuronic acid to form water soluble sulfate esters or glucuronides, and they are excreted as such.

Conjugated mostly in liver but also in kidney. /Human, oral/

In the present study the metabolism of prednisolone in the isolated, perfused, dual recirculating human placental lobule was reexamined, using a perfusate based on tissue culture medium 199. Four metabolites were identified in both the maternal and fetal compartments in 6 hr perfusions by comparison of relative retention times measured by HPLC and capillary GC and of mass spectra recorded by capillary GC/MS with those of authentic reference standards. The steroids were derivatized as the MO-TMS ethers for mass spectral measurements. Analysis of samples from five perfusion experiments resulted in the following percentage conversions after 6 hr perfusion (mean + or - standard deviation, maternal and fetal perfusate, respectively): prednisone (49.1 + or - 7.8, 49.1 + or - 6.6), 20 alpha-dihydroprednisone (0.84 + or - 0.29, 0.81 + or - 0.35), 20 beta-dihydroprednisone (39.1 + or - 6.7, 39.2 + or - 5.9), 20 beta-dihydroprednisolone (6.8 + or - 2.7, 6.3 + or - 1.6) and unmetabolized prednisolone (4.1 + or - 1.8, 4.6 + or - 2.1). No evidence was found for metabolites formed by 6 beta-hydroxylation or cleavage of the C17-C20 bond.

A randomized, four-way cross-over 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 as single, oral 10-mg tablet doses and as 10-mg zero-order 0.5-hour intravenous infusions. Comparable mean PN and PL maximum plasma concentrations (Cmax), times for Cmax, areas under the plasma concentration-time curves (AUC), and apparent elimination rate constants between tablet treatments demonstrated that PN and PL tablets were bioequivalent. Absolute bioavailability (F) determinations based on plasma PL concentrations were independent of which IV treatment was used as reference and indicated complete systemic availability of PL from both PN and PL tablets. However, F based on plasma PN data was contradictory. Using IV PN as reference, approximately 70% systemic availability was observed from both tablets, whereas using IV PL as reference, systemic availability was greater than unity. PN and PL are model compounds that exemplify the difficulties involved in accurately determining the relative and absolute bioavailability of substances that undergo reversible metabolism.

Prednisone, prednisolone, and methylprednisolone are currently administered in association with cyclosporin A in the postoperative treatment of transplant patients. The aim of this work was to evaluate the effects of these corticosteroids on the expression of several forms of cytochromes p450, including p450 1A2, 2D6, 2E1, and 3A, and on cyclosporin A oxidase activity in human liver. For this purpose, human hepatocytes prepared from lobectomies were maintained in culture in a serum-free medium, in collagen-coated dishes, for 96-144 hr, in the absence or presence of 50-100 uM corticosteroids, rifampicin, or dexamethasone. To mimic more closely the current clinical protocol, hepatocyte cultures were also co-treated with corticosteroids and cyclosporin A or ketoconazole (a selective inhibitor of cytochromes p450 3A). Cyclosporin A oxidase activity, intracellular retention of cyclosporin A oxidized metabolites within hepatocytes, accumulation of cytochromes p450 proteins and corresponding messages, and de novo synthesis and half-lives of these cytochromes p450 were measured in parallel in these cultures. Our results, obtained from seven different hepatocyte cultures, showed that 1) dexamethasone and prednisone, but not prednisolone or methylprednisolone, were inducers of cytochrome p450 3A, at the level of protein and mRNA accumulation, as well as of cyclosporin A oxidase activity, known to be predominantly catalyzed by these cytochromes p450; 2) although corticosteroids are known to be metabolized in human liver, notably by cytochrome p450 3A, partial or total inhibition of this cytochromes p450 by cyclosporin or ketoconazole, respectively, did not affect the inducing efficiency of these molecules; 3) corticosteroids did not affect the half-life of cytochrome p450 3A or the accumulation of other forms of cytochromes p450, including 1A2, 2D6, and 2E1; 4) chronic treatment of cells with cyclosporin did not affect cytochrome p450 3A accumulation; 5) corticosteroids were all competitive inhibitors of cyclosporin A oxidase in human liver microsomes, with Ki values of 61 + or - 12, 125 + or - 25, 190 + or - 38, and 210 + or - 42 uM for dexamethasone, prednisolone, prednisone, and methylprednisolone, respectively; and 6) chronic treatment of cells with corticosteroids did not influence the excretion of oxidized metabolites of cyclosporin from the cells.

9PHQ9Y1OLM

PREDNISOLONE

Established Pharmacologic Class [EPC] - Corticosteroid

Mechanisms of Action [MoA] - Corticosteroid Hormone Receptor Agonists

Prednisolone is a Corticosteroid. The mechanism of action of prednisolone is as a Corticosteroid Hormone Receptor Agonist.

PREDNISOLONE

Substances that reduce or suppress INFLAMMATION.

A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)

Oral prednisolone reaches a Cmax of 113-1343ng/mL with a Tmax of 1.0-2.6 hours. Oral prednisolone is approximately 70% bioavailable.

Prednisolone is over 98% eliminated in urine.

A 0.15mg/kg dose of prednisolone has a volume of distribution of 29.3L, while a 0.30mg/kg dose has a volume of distribution of 44.2L.

A 0.15mg/kg dose of prednisolone has a clearance of 0.09L/kg/h, while a 0.30mg/kg dose has a clearance of 0.12L/kg/h.

A randomized crossover study was conducted to compare the pharmacokinetics and pharmacodynamics of 30 mg prednisolone in a plain oral tablet (Precortisyl) with those of an enteric coated tablet (Deltacortril) in 8 patients (ages 63-81 yr) with chronic obstructive pulmonary disease and in 8 healthy males (ages 22-44 yr). Although drug absorption was considerably slower from the enteric coated tablet, peak plasma levels and total area under the concn-time curve were equivalent for the formulations. Adrenal suppression was significantly less in volunteers after enteric coated than after plain tablets. This difference was not significant in patients. Plasma cortisol levels declined more slowly after enteric coated tablets in both groups. Blood glucose levels increased over 8 hr in both groups. It was concluded that in patients with chronic obstructive pulmonary disease, peak plasma levels and total area under the concn-time curve of plain and enteric coated prednisolone tablets are equivalent; enteric coated tablets result in a lag in the decline of plasma cortisol and, in volunteers, a less marked suppression of cortisol.

The transfer of prednisolone to breast milk was studied in 3 nursing women (ages 28-37 yr) who received an intravenous injection of 50 mg prednisolone sodium phosphate (Hydeltrasol). Concn of prednisolone in milk declined more rapidly than in serum, but were similar to expected unbound serum levels. Milk levels ranged from about 15% to 40% of serum levels. The exchange between unbound drug in serum and breast milk appeared to be relatively rapid and bidirectional. An average of 0.025% (0.01-0.49%) of the prednisolone dose was recovered in milk. It was concluded that the transfer of prednisolone to breast milk does not appear to pose a clinically significant risk.

Medicine, also available in acetate.

...Commonly used to treat lymphoreticular neoplasms in combination with other drugs ... especially useful in treatment of leukemias and lymphomas of the central nervous system.

THERAP CAT: Glucocorticoid

THERAP CAT (VET): Glucocorticoid

For more Uses (Complete) data for PREDNISOLONE (6 total), please visit the HSDB record page.

Use (kg; approx.) in Germany (2009): >2500

From hydrocortisone by a microbiological process using Corynebacterium simplex, which selectively dehydrogenates cortisol at the 1 and 2 positions.

Preparation: A. Nobile, US 2837464; US 3134718 (1958, 1964, both to Schering)

Ophthalmic: Solution: 0.125% (0.11% of prednisolone phosphate) Inflamase Mild (with benzalkonium chloride), (Novartis); 1% (0.9% of prednisolone phosphate) AK-Pred (with benzalkonium chloride and sodium bisulfite), (Akorn), Inflamase Forte (with benzalkonium chloride), (Novartis), Prednisolone Sodium Phosphate Ophthalmic Solution, (Bausch & Lomb). /Prednisolone sodium phosphate/

Powder: Ophthalmic: Suspension: 0.12% Pred Mild (with benzalkonium chloride and sodium bisulfite), (Allergan); 1% Econopred Plus (with benzalkonium chloride), (Alcon), Pred Forte (with benzalkonium chloride and sodium bisulfite), (Allergan), Prednisolone Acetate Ophthalmic Suspension, (Falcon). /Prednisolone acetate/

Oral: Solution: 5 mg (of prednisolone) per 5 mL Pediapred (with methylparaben), (Celltech), Prednisolone Sodium Phosphate Oral Solution, (Ethex), Prednisolone Sodium Phosphate Oral Solution, (Hi-Tech), Prednisolone Sodium Phosphate Oral Solution, (Morton Grove), Prednisolone Sodium Phosphate Oral Solution, (Pharmaceutical Associates), Prednisolone Sodium Phosphate Oral Solution, (WE Pharmaceuticals); 15 mg (of prednisolone) per 5 mL Orapred (with alcohol 2% and povidone), (BioMarin), Prednisolone Sodium Phosphate Oral Solution, (Ethex), Prednisolone Sodium Phosphate Oral Solution, (Morton Grove), Prednisolone Sodium Phosphate Oral Solution, (Pharmaceutical Associates), Prednisolone Sodium Phosphate Oral Solution, (WE Pharmaceuticals). Tablets, orally disintegrating: 10 mg (of prednisolone) Orapred ODT (with crospovidone), (Alliant); 15 mg (of prednisolone) Orapred ODT (with crospovidone), (Alliant); 30 mg (of prednisolone) Orapred ODT (with crospovidone), (Alliant). /Prednisolone sodium phosphate/

Oral: Solution: 5 mg/5 mL Prednisolone Syrup, (Ethex), Prednisolone Syrup, (Hi-Tech), Prednisolone Syrup, (Morton Grove), Prednisolone Syrup, (Paddock), Prednisolone Syrup, (Pharmaceutical Associates), Prednisolone Syrup, (WE Pharmaceuticals); 15 mg/5 mL Prednisolone Syrup, (Alpharma), Prednisolone Syrup, (Ethex), Prednisolone Syrup, (Hi-Tech), Prednisolone Syrup, (Morton Grove), Prednisolone Syrup, (Pharmaceutical Associates), Prednisolone Syrup, (Teva), Prednisolone Syrup, (Watson), Prednisolone Syrup, (WE Pharmaceuticals), Prelone Syrup (with alcohol 5% and propylene glycol), (Aero). Tablets: 5 mg Prednisolone Tablets, (Watson).

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Pharmaceuticals

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Pregna-1,4-diene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-: ACTIVE

Synthetic corticosteroid

Generic name for an analog of hydrocortisone.