药品详细
Nitisinone(Nitisinone)
化学结构式图
中文名
Nitisinone
英文名
Nitisinone
分子式
C14H10F3NO5
化学名
2-{[2-nitro-4-(trifluoromethyl)phenyl]carbonyl}cyclohexane-1,3-dione
分子量
Average: 329.2281
Monoisotopic: 329.05110705
Monoisotopic: 329.05110705
CAS号
104206-65-7
ATC分类
A16A Other Alimentary Tract and Metabolism Products
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍
Nitisinone is a synthetic reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase. It is used in the treatment of hereditary tyrosinemia type 1. It is sold under the brand name Orfadin. [Wikipedia]
生产厂家
- Rare disease therapeutics inc
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference | Not Available |
剂型
规格
化合物类型
| Type | small molecule |
| Classes |
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| Substructures |
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适应症
药理
| Indication | Used as an adjunct to dietary restriction of tyrosine and phenylalanine in the treatment of hereditary tyrosinemia type 1. |
| Pharmacodynamics | Hereditary tyrosinemia type 1 occurs due to a deficiency in fumarylacetoacetase (FAH), the final enzyme in the tyrosine catabolic pathway. Nitisinone inhibits catabolism of tyrosine by preventing the catabolic intermediates. In patients with HT-1, these catabolic intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate, which are responsible for the observed liver and kidney toxicity. Succinylacetone can also inhibit the porphyrin synthesis pathway leading to the accumulation of 5-aminolevulinate, a neurotoxin responsible for the porphyric crises characteristic of HT-1. |
| Mechanism of action | Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of fumarylacetoacetate hydrolyase (FAH) in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with hereditary tyrosinemia type 1 (HT-1), nitisinone prevents the accumulation of the catabolic intermediates maleylacetoacetate and fumarylacetoacetate. |
| Absorption | The capsule and liquid formulations are bioequivalent in both the plasma concentration-time curve and maximum plasma concentration (Cmax). |
| Volume of distribution | Not Available |
| Protein binding | Not Available |
| Metabolism |
Not Available
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| Route of elimination | Not Available |
| Half life | ~54 hours |
| Clearance | Not Available |
| Toxicity | Side effects include elevated plasma levels of this amino acid, hepatic and liver failure. |
| 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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药物相互作用
食物相互作用
Not Available
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