Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
메틸프레드니솔론
메틸프레드니솔론 · MEDROL · Methylprednisolone for system suitability A CRS · Metllylpredllisolone · a-methapred · Methylprednisolone CRS · U 7532 · MEPRDL
식별자 및 물리적 특성
| CAS No. | 83-43-2 |
|---|---|
| 분자식 | C22H30O5 |
| 평균 분자량 | 374.5 g/mol |
| 단동위원소 질량 | 374.20932406 g/mol |
| SMILES | C[C@H]1C[C@@H]2[C@H]([C@@H](O)C[C@@]3(C)[C@H]2CC[C@]3(O)C(=O)CO)[C@@]2(C)C=CC(=O)C=C12 |
| InChIKey | VHRSUDSXCMQTMA-PJHHCJLFSA-N |
| PubChem CID | 6741 |
| ChEMBL | CHEMBL650 |
| ChEBI | CHEBI:6888 |
| EC No. | 201-476-4 |
| DTXSID | DTXSID7023300 |
| 현지명 | 메틸프레드니솔론 |
화학 및 물리적 성질
| XLogP | 1.9 |
|---|---|
| 극성 표면적 | 94.8 |
| 수소 결합 공여자 수 | 3 |
| 수소 결합 수용자 수 | 5 |
| 회전 가능 결합 수 | 2 |
| 무거운 원자 수 | 27 |
| 형식 전하 | 0 |
| 복잡도 | 754 |
| 의약품 | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Steroids |
| 지질 | Lipids -> Sterol Lipids [ST] -> Steroids [ST02] -> C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives [ST0203] |
| SpringerMaterials Properties | Magnetic anisotropy |
| LogP(분배 계수) | 1.52.12 |
| 냄새 | Odorless |
| Color/Form | CrystalsWhite to practically white crystalline powder |
| 용해도 | MW 416.51, crystals, MP 205-208 °C, specific optical rotation: 101 deg at 20 °C (dioxane), uv max (95% ethanol): 243 nm (alpha m 14825), Sol in dioxanesparingly sol in acetone, alcohol, chloroform, methanolslightly sol in ether. Practically insol in water. /21-acetate/SOL IN WATER /METHYLPREDNISOLONE 21-SUCCINATE SODIUM SALT/Sparingly sol in alc, dioxane, methanolslightly sol in acetone, chloroformvery slightly sol in ether.In water, 1.20X10+2 mg/L at 25 °C1.09e-01 g/L에 용해됨 클로로포름/메탄올(9:1): 50mg/mL, 투명, 희미한 노란색 |
| Human Drugs | Breast FeedingLactationMilk, HumanCorticosteroids, SystemicGlucocorticoidsAnti-Inflammatory AgentsFDA approved drugs -> Active ingredientHormones and antihormones |
| Animal Drugs | Active Ingredients (Methylprednisolone) -> FDA GreenbookPharmaceuticals -> Animal Drugs -> Approved in Taiwan |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| 녹는점 | 228-237 °C232.5 °C228-237°C (dec.) |
| Optical Rotation | Specific optical rotation: +83 deg at 20 °C/D (dioxane)max absorption (95% ethanol): 243 nm (alpha(m)= 14,875) |
| 끓는 점 | 423.47°C (rough estimate) |
| 밀도 | 1.0868 (rough estimate) |
| 굴절률 | 82 ° (C=1, Dioxane) |
| 저장 조건 | 0-6°C |
| pKa(산도 계수) | 12.46±0.70(Predicted) |
| 물리적 상태 | Solid |
| 색상 | 흰색에서 황백색까지 |
| 용해도 | 0.12g/L(25℃) |
| Merck | 14,6111 |
| BRN | 2340300 |
| 헨리 상수 | 2.7×102 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 2 or 4 |
| 주요 응용 | 제약소분자 약용 |
| InChIKey | VHRSUDSXCMQTMA-PJHHCJLFSA-N |
| SMILES | [H][C@@]12C[C@H](C)C3=CC(=O)C=C[C@]3(C)[C@@]1([H])[C@@H](O)C[C@@]4(C)[C@@]2([H])CC[C@]4(O)C(=O)CO |
| NIST | 1,4-Pregnadiene-3,20-dione, 11beta,17alpha,21-trihydroxy-6alpha-methyl-(83-43-2) |
| EPA | Pregna-1,4-diene-3,20-dione, 11,17,21-trihydroxy-6-methyl-, (6.alpha.,11.beta.)- (83-43-2) |
화학적 성질
White to Off-White Crystalline Powder
안전 및 규제
| GHS 분류 | This chemical does not meet GHS hazard criteria for 0.9% (1 of 110) of reports.DangerH302 (16.4%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P264, P270, P280, P301+P317, P302+P352, P317, P318, P319, P321, P330, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 110 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 규제 정보 | Status: Active Update: 22-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/16624Methylprednisolone: Does not have an individual approval but may be used under an appropriate group standard |
| 기타 안전 정보 | IMAP assessments - Pregna-1,4-diene-3,20-dione, 11,17,21-trihydroxy-6-methyl-,(6.alpha.,11.beta.)-: Environment tier I assessment |
| FDA 요건 | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl methylprednisolone 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 methylprednisolone acetate approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Methylprednisolone acetate/The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl methylprednisolone sodium succinate approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Methylprednisolone sodium succinate/The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Methylprednisolone is included on this list.For more FDA Requirements (Complete) data for METHYLPREDNISOLONE (7 total), please visit the HSDB record page. |
| Hazard Classes and Categories | Acute Tox. 4 (16.4%) |
| 보관 조건 | Commercially available preparations of methylprednisolone should be stored at a temperature less than 40 °C, preferably between 15-30 °Cfreezing of methylprednisolone acetate sterile suspension should be avoided. Unreconstituted methylprednisolone sodium succinate sterile powder and reconstituted solutions of the drug, and methylprednisolone sodium acetate solution for injection should be stored at a controlled room temperature of 20-25 °C. |
| 처리 방법 | 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. |
| Allowable Tolerances | A tolerance is established for negligible residues of methylprednisolone in milk at 10 parts per billion. |
| 상호 작용 | PHENYTOIN IS ... KNOWN TO INCR METABOLISM OF ... METHYLPREDNISOLONE IN HUMANS.SYSTEMIC EFFECTS OF ADMIN CORTICOSTEROIDS /METHYLPREDNISOLONE/ ... MAY BE DIMINISHED BY LARGE DOSES OF BARBITURATES SUCH AS PHENOBARBITAL.HYPERGLYCEMIC ACTION OF CORTISONE /METHYLPREDNISOLONE/ MAY OFFSET HYPOGLYCEMIC ACTION OF CHLORPROPAMIDE.Methylprednisolone clearance was reduced in asthmatic patients also taking troleandomycin.For more Interactions (Complete) data for METHYLPREDNISOLONE (25 total), please visit the HSDB record page. |
| 환경 거동 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 310(SRC), determined from a water solubility of 1.2X10+2 mg/L(2) and a regression-derived equation(3), indicates that methylprednisolone is expected to have moderate mobility in soil(SRC). Volatilization of methylprednisolone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.6X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Methylprednisolone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.9X10-14 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data for methylprednisolone were not available(SRC, 2007).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 310(SRC), determined from a water solubility of 1.20X10+2 mg/L(2) and a regression-derived equation(3), indicates that methylprednisolone is 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 3.6X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 41(SRC), from its water solubility(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data for methylprednisolone were not available(SRC, 2007).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), methylprednisolone, which has an estimated vapor pressure of 3.9X10-14 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 methylprednisolone may be removed from the air by wet or dry deposition(SRC). Methylprednisolone absorbs UV light at a maximum of 243 nm(3) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| 유해 작용 | The significant adverse effects of glucocorticoids stem from their hormonal actions, which can result in iatrogenic Cushing syndrome. Facial rounding, puffiness, fat deposition, and plethora (moon facies) are usually apparent. Fat redistributes from the extremities to the trunk, the back of the neck, and the supraclavicular fossae. Fine hair grows more quickly on the face, thighs, and trunk. Steroid-induced punctate acne may appear, and insomnia and increased appetite may be observed. With concurrent use of methylprednisolone, protein catabolism continues, diverting amino acids to glucose production, thus increasing the need for insulin and resulting in weight gain. Myopathy and muscle wasting can occur, as well as skin thinning, with striae and bruising. Hyperglycemia and osteoporosis can develop, as well as diabetes and aseptic necrosis of the hip. |
| Milk Concentrations | Corticosteroids may be distributed into milk ... . /Corticosteroids/ |
| 독성 요약 | Signs and Symptoms of Overdose |
| Soil Adsorption/Mobility | The Koc of methylprednisolone is estimated as 310(SRC), using a water solubility of 1.20X10+2 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that methylprednisolone is expected to have moderate mobility in soil. |
| Human Toxicity Excerpts | /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/ A 16-year-old poorly compliant, steroid-dependent subject with asthma received two courses of high-dose intravenous methylprednisolone during a 3-week period, followed by a tapering schedule of oral prednisone. During this time, she was exposed to chickenpox. She subsequently developed a classic varicella rash, sever back pain, rapidly progressive hepatic failure, pneumonitis, and encephalopathy. Death ensued 3 days after the onset of the rash. Evidence of disseminated varicella infection was confirmed at autopsy. This case illustrates that a small number of subjects with severe asthma receiving high-dose corticosteroids need to be considered as a separate, high-risk group for developing disseminated varicella. We recommend that the immune status of these patients to varicella-zoster virus be assessed by a serum titer. If these patients are nonimmune, they would be candidates for varicella-zoster immune globulin on exposure, and for acyclovir therapy should varicella dissemination occur./CASE REPORTS/ Two patients with recalcitrant ocular hypertension persisting 6 and 4 months, respectively, after periocular injection of methylprednisolone acetate despite maximum medical therapy /were described/. White sub-Tenon's plaques of residual methylprednisolone acetate were excised surgically and analyzed for steroid activity using spectrophotometry. In both cases, intraocular pressure was normalized promptly after surgical removal of visible steroid. In both instances, biochemical analysis of the excised samples revealed residual steroid. Surgical removal of a residual methylprednisolone depot is an effective management choice in patients developing persistent intraocular pressure elevation after periocular injection. /Methylprednisolone acetate//CASE REPORTS/ A 47-year-old woman was admitted to our clinic with weakness, fatigue, pruritus, and scleral icterus that had developed 10 days prior to presentation. She had been taking topiramate for one year for treatment of chronic isolated central nervous system vasculitis. One week before her symptoms developed, she had completed a self-prescribed 7 day course of oral methylprednisolone for treatment of left arm weakness. She believed that methylprednisolone was appropriate since it had been used previously for acute episodes of vasculitis. Results of liver function tests performed on admission were alanine aminotransferase 2478 U/L, aspartate aminotransferase 1600 U/L, total bilirubin 10 mg/dL, direct bilirubin 8 mg/dL, alkaline phosphatase 138 U/L, and gamma-glutamyl transferase 242 U/L. Topiramate and methylprednisolone were the only drugs she had been taking before admission, and no other causes of liver dysfunction (eg, infection, ischemia, systemic disease) were identified. Topiramate was stopped, and enzyme levels decreased to normal values within 45 days without treatment. There had been no increase in enzyme levels during hospitalization upon the accidental use of topiramate. Based on the history and laboratory findings, the final diagnosis was mixed hepatocellular and cholestatic liver injury caused by methylprednisolone. DISCUSSION: Steroids have rarely been associated with hepatotoxicitymoreover, they are the treatment of choice for severe hepatitis. To date, only 2 cases of methylprednisolone-induced hepatotoxicity have previously been reported. Our case is similar to those with regard to mixed hepatocellular and cholestatic liver injury. Resolution of the hepatotoxicity occurred after discontinuation of the drug, with conservative treatment measures. An objective causality assessment based on the Naranjo scale suggests that hepatotoxicity was probably related to methylprednisolone. Although rare, hepatotoxicity related to methylprednisolone should be considered in patients who develop elevated enzyme levels while receiving this steroid.For more Human Toxicity Excerpts (Complete) data for METHYLPREDNISOLONE (12 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Methylprednisolone's production and use as an antiinflammatory glucocorticoid in human and veterinary medicine(1,2) may result in its release to the environment through various waste streams(SRC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)MethylprednisolonevLess-DILI-concern3Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Environmental Bioconcentration | An estimated BCF of 41 was calculated for methylprednisolone(SRC), using a water solubility of 1.20X10+2 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC), provided the compound is not metabolized by the organism(SRC). |
| Volatilization from Water/Soil | The Henry's Law constant for methylprednisolone is estimated as 3.6X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that methylprednisolone is expected to be essentially nonvolatile from water surfaces(2). Methylprednisolone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.9X10-14 mm Hg(SRC), determined from a fragment constant method(3). |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Repeated dose toxicity studies were carried out with methylprednisolone in dogs using daily oral doses of 0, 2.5 and 5 mg/kg body weight/day for 42 days and daily intramuscular administration of 1.1 to 1.5 mg/kg body weight/day methylprednisolone for 5 weeks. In a special study to investigate adrenal gland function, groups of dogs were dosed orally with 2 or 4 mg/day or intramuscularly with 2.5 mg/kg body weight once a week. The main effects in these studies were reduced body weight, skeletal muscle atrophy, increased glycogen deposition in the liver and adrenal atrophy./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ A 14 week repeated dose toxicity study was carried out in Sprague-Dawley rats given daily subcutaneous doses of 0, 0.4, 4, 40 or 400 ug/kg body weight/day of methylprednisolone aceponate. Body weight gain and food consumption were reduced in males given 40 ug/kg body weight and above and females given 400 ug/kg body weight and above. Leucocyte counts were reduced in both sexes given 400 ug/kg body weight and bone marrow lymphocytes were reduced in males given 400 ug/kg body weight and females given 4 ug/kg body weight and above. Changes in serum clinical chemistry values at 400 ug/kg were indicative of effects on the liver and kidney. Atrophy of the thymus and adrenal glands was observed in the 400 ug/kg body weight group at necropsy. The NOEL was 0.4 ug/kg body weight/day. /Methylprednisolone aceponate//LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A 52 week repeated-dose toxicity study was carried out in the Sprague Dawley rat using subcutaneous doses of 0, 0.16, 0.8, 4, 20 or 100 ug/kg body weight methylprednisolone aceponate. At 100 ug/kg body weight, the main effects were reduced body weight and food consumption, reduced erythrocyte, hematocrit and lymphocyte counts and atrophy of the spleen and adrenals. At 20 ug/kg body weight, body weight gain and food consumption were reduced and there were some minor effects on oran weight and clinical chemistry values. The NOEL was 4 ug/kg body weight/day. /Methylprednisolone aceponate//LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ A fertility study of methylprednisolone aceponate, anti-inflammatory corticosteroid, was performed using Jcl:SD rats at doses of 0.004, 0.02 and 0.1 mg/kg body wt. Methylprednisolone aceponate was administered sc to male rats from 60 days before mating until successful copulation, and to female rats from 14 days before mating until day 7 of gestation. On day 21 of gestation, all dams were killed and their fetuses were examined for external, internal and skeletal abnormalities. The following results were obtained. Suppression of body wt gain and food consumption, and increase in dead embryos and fetuses were observed in the 0.02 and 0.1 mg/kg groups. From the above results, the no-effect dose of methylprednisolone aceponate was estimated to be 0.004 mg/kg body wt for general toxicity in parent animals, 0.1 mg/kg body wt for reproductive toxicity in parent animals, and 0.004 mg/kg body wt for developmental toxicity in the fetuses. /Methylprednisolone aceponate/For more Non-Human Toxicity Excerpts (Complete) data for METHYLPREDNISOLONE (9 total), please visit the HSDB record page. |
| 수질 위해 등급(WGK) | 2 |
| TSCA 등재 상태 | TSCA listed |
| RTECS 번호 | TU4146000 |
| 관세 코드 | 2937290000 |
| 위험 문구(R) | 36/37/38 |
| 위험 표시 | Xi |
| 안전 문구(S) | 22-36-26 |
| F 고인화성물질 | 8-10-23 |
| 위험 등급 | Repr. 1BSTOT RE 2 |
| 저장 분류 | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| 유해 물질 데이터 | 83-43-2(Hazardous Substances Data) |
용도
일반 설명
Methylprednisolone, 11β,17,21-trihydroxy-6α-methyl-1,4-pregnadiene-3,20-dione, isavailable unmodified or as ester derivatives.Methylprednisolone acetate, USPMethylprednisolone sodium succinate, USP.