Agrylin(Anagrelide Capsules)-安归宁(阿那格雷胶囊）
药品名称
中文药名: 阿那格雷(安归宁)
中文别名：氯喹咪唑酮、盐酸阿那格利
英文名：Anagrelide
缩写： Agrylin
化学合成，结构为活性奎宁唑啉。
简介
在欧洲上市的西尔公司在美国和加拿大销售阿那格雷的商标为Agrylin, 在欧洲销售的商标为Xagrid。Agrylin是治疗原发性血小板血症（ET）的药物，ET是骨髓的一种慢性疾病，该病与血小板生成增多相关。
作用机制
本药原用作抑制血小板聚集，有抗血栓效果，但近年应用低剂量时发现其有降低血小板作用。作用机制可能是影响巨核细胞细胞周期后期（有丝分裂后）分化成熟，使血小板生成减少。不影响DNA、RNA的合成及巨核细胞增殖分裂，因而无潜在致癌性。
相互作用
硫糖铝可以干扰安归宁吸收。
适应症
美国FDA批准用于特发性血小板增多症及真性红细胞增多症并发血小板增多。但对于由其他骨髓增殖性疾病如骨髓纤维化和骨髓增生异常综合征伴随血小板增高亦可应用。
禁忌
1、 对安归宁过敏者禁用。
2、 妊娠或有预期妊娠妇女禁用。
3、 有严重心血管及肝肾疾病者慎用。
不良反应
1、 心血管系统：乏力、心悸、水肿，个别可发生心律紊乱。
2、 消化系统：腹痛、恶心、腹胀，发生率为10%左右。肝脏转氨酶升高。
3、 呼吸系统：气短、肺纤维化和肺浸润。
4、 神经系统：头疼（发生率在亚洲可达一半），眩晕、无力，视物模糊或视力有严重影响。
注意事项
1、告知女性患者服药期间应采取避孕措施。
2、告知患者服药初期可能会发生头疼、心悸，多于用药第2周内出现，继续用药可逐渐消失，症状明显可对症用止痛药。
3、有严重心脑血管病患者用时必须定期监测心脏功能，因本药可有水潴留作用。
4、血小板降低症状多在用药1周
贮存
15~20℃，避光。

AGRYLIN- anagrelide hydrochloride capsule
Shire US Manufacturing Inc.
DESCRIPTIONName: AGRYLIN ® (anagrelide hydrochloride)
Dosage Form: 0.5 mg capsules for oral administration
Active Ingredient: AGRYLIN ® Capsules contain 0.5 mg of anagrelide base (as anagrelide hydrochloride).
Inactive Ingredients: Anhydrous Lactose NF, Crospovidone NF, Lactose Monohydrate NF, Magnesium stearate NF, Microcrystalline cellulose NF, Povidone USP.
Pharmacological Classification: Platelet-reducing agent.
Chemical Name: 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one monohydrochloride monohydrate.
Molecular formula: C10 H7 Cl2 N3 O•HCl•H2 O
Molecular weight: 310.55Structural formula:



Appearance: Off-white powder
Solubility: Water……………………….. Very slightly soluble
Dimethyl Sulfoxide………… Sparingly soluble
Dimethylformamide………… Sparingly soluble
CLINICAL PHARMACOLOGYThe mechanism by which anagrelide reduces blood platelet count is still under investigation. Studies in patients support a hypothesis of dose-related reduction in platelet production resulting from a decrease in megakaryocyte hypermaturation. In blood withdrawn from normal volunteers treated with anagrelide, a disruption was found in the postmitotic phase of megakaryocyte development and a reduction in megakaryocyte size and ploidy. At therapeutic doses, anagrelide does not produce significant changes in white cell counts or coagulation parameters, and may have a small, but clinically insignificant effect on red cell parameters. Anagrelide inhibits cyclic AMP phosphodiesterase III (PDEIII). PDEIII inhibitors can also inhibit platelet aggregation. However, significant inhibition of platelet aggregation is observed only at doses of anagrelide higher than those required to reduce platelet count.
Following oral administration of 14 C-anagrelide in people, more than 70% of radioactivity was recovered in urine. Based on limited data, there appears to be a trend toward dose linearity between doses of 0.5 mg and 2.0 mg. At fasting and at a dose of 0.5 mg of anagrelide, the plasma half-life is 1.3 hours. The available plasma concentration time data at steady state in patients showed that anagrelide does not accumulate in plasma after repeated administration.
Two major metabolite