Prednisolone   中文名称: 泼尼松龙

泼尼松龙（0.002-10 μg/mL；3 天）抑制人白细胞有丝分裂[4]。

泼尼松龙（5 mg/kg/天；口服；每周 6 天，持续 72 周）可显着降低患有肾病的小鼠的死亡率[3]。

Animal/Disease Models: NZB/NZW mice, immune nephritis model[3]
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
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.
The pharmacokinetics of prednisolone after oral and intravenous administration of 10 and 20 mg have been studied. Serum protein binding of prednisolone was also measured after the iv injections. The bioavailability after oral administration was 84.5% after 10 mg and 77.6% after 20 mg (p>0.05). Dose dependent pharmacokinetics were found, the VDss and Clt being significantly larger (p<0.01) after 20 mg iv than after 10 mg iv. The protein binding of prednisolone in all subjects was non-linear, and is the most likely cause of the dose dependent pharmacokinetics, as there was no dose dependent variation in elimination half-time.
Doses of 16, 32, 48 and 64 mg prednisolone were administered intravenously to normal volunteers who also received 100 prednisolone orally. Plasma prednisolone concentrations were estimated by quantitative thin layer chromatography. The bioavailability fraction was 1.063 +/- 0.154 (s.d.) indicating complete availability of prednisolone following oral administration. 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. The mean systemic clearance over all doses was 0.104 +/- 0.034 (s.d) L/hr/kg. There was no evidence of a dose-related change in clearance or in the apparent volume of distribution (overall mean 0.588 +/- 0.152 L/kg). The area under the plasma concentration-time curve was linearly related to dose. Plasma concentration-time curves normalised for dose were superimposable. It was concluded that over the dose range investigated, non-linear pharmacokinetic behavior had not been demonstrated in this group of normal volunteers.
For more Absorption, Distribution and Excretion (Complete) data for PREDNISOLONE (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
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.

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Biological Half-Life
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.

Interactions
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.

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Non-Human Toxicity Values
LD50 Mouse ip > 1000 mg/kg body weight /Prednisolone acetate/
LD Mouse ip 767 mg/kg body weight
LD50 Swiss mouse oral 1680 mg/kg body weight
LD50 Sherman rat (male) sc 147 mg/kg body weight

Proc Soc Exp Biol Med.1994 Mar;205(3):220-9;J Clin Invest.1993 Sep;92(3):1534-42.

Therapeutic Uses
Anti-Inflammatory Agents, Steroidal; Antineoplastic Agents, Hormonal; Glucocorticoids, Synthetic
Ophthalmic corticosteroids are indicated in the treatment of corticosteroid-responsive allergic and inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe. /Corticosteroids (Ophthalmic); Included in US product labeling/
VET: Hormonal therapy for neoplasia commonly involves the use of glucocorticoids. Direct antitumor effects are related to their lympholytic properties; glucocorticoids can inhibit mitosis, RNA synthesis, and protein synthesis in sensitive lymphocytes. Glucocorticoids are considered cell-cycle nonspecific and are often used in chemotherapeutic protocols after induction by another agent. Prednisolone /is/ commonly used to treat lymphoreticular neoplasms in combination with other drugs. Because /it/ readily enters the CSF, ... prednisolone /is/ especially useful in treatment of leukemias and lymphomas of the CNS.
Indicated in a wide range of endocrine, rheumatic, allergic, dermatologic, respiratory, hematologic, neoplastic, and other disorders.
For more Therapeutic Uses (Complete) data for PREDNISOLONE (28 total), please visit the HSDB record page.

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Drug Warnings
VET: IT OFTEN MAY BE CONTRAINDICATED IN CONGESTIVE HEART FAILURE, DIABETES OR OSTEOPOROSIS. EXCEPT FOR EMERGENCY LIFE SAVING USE, IT SHOULD BE OMITTED IN TUBERCULOSIS, CHRONIC NEPHRITIS, CUSHINGOID SYNDROMES, & PEPTIC ULCER CASES.
Side effects and compliance were examined in 63 pediatric patients (ages 10 mo-14 yr) with acute asthma who received an oral dose of 1-2 mg/kg prednisolone (Solone; Panafcortelone) as a whole or crushed tablet or in liquid form for 7 days. Up to 44% of patients either refused to take or vomited the drug on the first day. Improved acceptability of prednisolone occurred with time, but prescribing practices indicated short-term treatment of 1 to 4 days was common. Abdominal pain and mood changes occurred in 19% and 80% of patients, respectively, at some stage of the study period. It was concluded that oral prednisolone is poorly tolerated in pediatric patients and its use may lead to suboptimal therapy.
Glucocorticoid use in children is not only associated with the side effects which are seen in adults, but also with severe adverse effects on statural growth. As little as 2.5-5.0 mg prednisolone/day can cause a retardation in statural growth. A direct relationship exists between the dose of glucocorticoid used and statural growth. The use of knemometry, a sensitive technique for measuring the growth of long bones in children has increased the accuracy of growth rate measurements. Many factors, such as disease process, sex, daily vs alternate day therapy, ethnic variations or whether the patient has been immobilized must be considered when evaluating the effects on stature of a particular glucocorticoid.
RESULTS FROM CONTROLLED TRIAL, INDICATE THAT PREDNISOLONE TREATMENT IS NOT BENEFICIAL & CAN BE DETRIMENTAL IN ACUTE NEUROPATHY OF UNDETERMINED ETIOLOGY.
For more Drug Warnings (Complete) data for PREDNISOLONE (48 total), please visit the HSDB record page.

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Pharmacodynamics
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.

C21H28O5

360.44

360.193

50-24-8

Prednisolone;50-24-8

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

94.83

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)

配方 1 中的溶解度: ≥ 2.08 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (5.77 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。