药品详细
Budesonide(布地奈德)
化学结构式图
中文名
布地奈德
英文名
Budesonide
分子式
C25H34O6
化学名
(1S,2S,4R,8S,9S,11S,12S,13R)-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-propyl-5,7-dioxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosa-14,17-dien-16-one
分子量
Average: 430.5339
Monoisotopic: 430.23553882
Monoisotopic: 430.23553882
CAS号
51333-22-3
ATC分类
A07E Intestinal Antiinflammatory Agents;D07A 未知;R01A 未知;R03B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍
Budesonide is a glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [PubChem] The extended release oral tablet, marketed as Uceris, was FDA approved on January 14, 2013 for the management of ulcerative colitis. Budesonide is provided as a mixture of two epimers (22R and 22S). Interestingly, the 22R form is two times more active than the 22S epimer. The two forms do not interconvert.
生产厂家
- Apotex inc
- Astrazeneca lp
- Astrazeneca pharmaceuticals lp
- Teva parenteral medicines inc
封装厂家
- 3M Health Care
- A-S Medication Solutions LLC
- Astra Pharma Inc.
- AstraZeneca Inc.
- Dispensing Solutions
- Galderma Laboratories
- Ivax Pharmaceuticals
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Physicians Total Care Inc.
- Prometheus Laboratories Inc.
- Redpharm Drug
- Spectrum Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
参考
| Synthesis Reference | Not Available |
| General Reference | Not Available |
剂型
规格
化合物类型
| Type | small molecule |
| Classes | Not Available |
| Substructures | Not Available |
适应症
药理
| Indication | The oral capsule is used for the treatment of mild to moderate active Crohn's disease. The oral tablet is used for induction of remission in patients with active, mild to moderate ulcerative colitis. The oral inhalation formulation is used for the treatment of asthma, non-infectious rhinitis (including hay fever and other allergies), and for treatment and prevention of nasal polyposis. | ||||||||||||
| Pharmacodynamics | Budesonide has a high glucocorticoid effect and a weak mineralocorticoid effect. It binds to the glucocorticoid receptor with a higher binding affinity than cortisol and prednisolone. When budesonide is systemically administered, suppression of endogenous cortisol concentrations and an impairment of the hypothalamus-pituitary-adrenal (HPA) axis function has been observed. Furthermore, a decrease in airway reactivity to histamine and other entities has been observed with the inhaled formulation. Generally, the inhaled formulation has a rapid onset action and improvement in asthma control can occur within 24 hours of initiation of treatment. | ||||||||||||
| Mechanism of action | Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. The precise mechanism of corticosteroid actions on inflammation in asthma, Crohn's disease, or ulcerative colitis is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of inhibitory activities against multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic-mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in the aforementioned diseases. Because budesonide undergoes significant first-pass elimination, the both oral preparations are formulated as an extended release tablet. As a result, budesonide release is delyaed until exposure to a pH ≥ 7 in the small intestine. | ||||||||||||
| Absorption | Absorption is complete following oral administration. The pharmacokinetic parameters of the inhaled powder formulation are as follows: Tmax = 30 minutes; Absolute systemic availability = 39%. When a single oral administration of 9 mg of Uceris are given, the pharmacokinetic parameters are as follows: Tmax = 13.3 ± 5.9 hours; Cmax = 1.35 ± 0.96 ng/mL; AUC = 16.43 ± 10.52 ng·hr/mL. It is important to note that the parameters have a high degree of variability. When a single oral administration of Entocort EC are given, the pharmacokinetic parameters are as follows: Tmax = 3- 600 minutes; Cmax = 5 nmol/L; AUC = 30 nmol•hr/L. | ||||||||||||
| Volume of distribution | Tablet and capsule, healthy subjects and patients = 2.2 – 3.9 L/kg; |
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| Protein binding | 85-90% protein bound. | ||||||||||||
| Metabolism |
Following absorption, budesonide is subject to high first pass metabolism (80-90%). Budesonide is rapidly and extensively biotransformed, mainly by CYP3A4, to its 2 major metabolites, 6b-hydroxybudesonide and 16a- hydroxyprednisolone. The glucocorticoid activity of these metabolites is negligible (<1/100) in relation to that of the parent compound.
Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.
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| Route of elimination | Budesonide is excreted in urine and feces in the form of metabolites. Approximately 60% of an intravenous radiolabelled dose was recovered in the urine. No unchanged budesonide was detected in the urine. | ||||||||||||
| Half life | Following IV administration of budesonide, the elimination half-life is 2.0 to 3.6 hours. This value does not differ between healthy adults and patients with Crohn’s disease. | ||||||||||||
| Clearance | Plasma clearance, tablet = 0.9 – 1.8 L/min; |
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| Toxicity | Single oral doses of 200 and 400 mg/kg were lethal in female and male mice, respectively. The signs of acute toxicity were decreased motor activity, piloerection and generalized edema. | ||||||||||||
| Affected organisms |
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| Pathways | Not Available | ||||||||||||
理化性质
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| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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药物相互作用
| Drug | Interaction |
|---|---|
| Bicalutamide | CYP3A4 Inhibitors like bicalutamide may increase the serum concentration of budesonide. The clinical significance of this interaction is greater for oral budesonide than for orally inhaled budesonide. Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. |
| Clotrimazole | CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Any patient receiving both budesonide and a moderate CYP3A4 inhibitor should be monitored closely for signs/symptoms of corticosteroid excess. |
| Conivaptan | CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). onsider reducing the oral budesonide dose when used together with a strong CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Any patient receiving both budesonide and a strong CYP3A4 inhibitor should be monitored closely for signs/symptoms of corticosteroid excess. |
| Itraconazole | Itraconazole may increase levels/effect of budesonide. |
| Ketoconazole | Ketoconazole may increase levels/effect of budesonide. |
| Telithromycin | Telithromycin may reduce clearance of Budesonide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Budesonide if Telithromycin is initiated, discontinued or dose changed. |
| Tipranavir | Tipranavir may increase the plasma concentration of Budesonide. Monitor for toxic Budesonide effects during concomitant administration. |
| Voriconazole | Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of budesonide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of budesonide if voriconazole is initiated, discontinued or dose changed. |
食物相互作用
- A mean delay in time to peak concentration of 2.5 hours is observed with the intake of a high-fat meal, with no significant differences in AUC.
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