8月1日宣布，Zavesca(miglustat)(I)胶囊已获FDA批准。它是第一个用于治疗I型Gaucher病(一种葡糖脑苷脂代谢的遗传病)的口服治疗选择。目前的治疗包括酶替代治疗(ERT)需要每月静脉滴注2次。(Ⅰ)是一类称为底物还原治疗(SRT)新治疗药的第一个化合物，它能通过减少糖鞘脂(GSL)的生成将它们的数目降低到能有效地被细胞内天然存在的葡糖脑苷脂酶清除的水平。 FDA批准的适应症是，用于治疗酶替代治疗不再是治疗选择(如由于禁忌例如变态反应、过敏反应或难于静脉给药等)的轻到中度Ⅰ型Gaucher病成人患者。可能或已妊娠的妇女不应用此药。 此药已在欧盟获准，并已在英国和德国销售。预计它将于今年晚些时候在美国推出。 Generic Name for ZAVESCA Miglustat 100mg; caps. Legal Classification: Rx Pharmacological Class for ZAVESCA Glucosylceramide synthase inhibitor. Manufacturer of ZAVESCA Actelion Pharmaceuticals   Indications for ZAVESCA Mild to moderate type 1 Gaucher disease when enzyme replacement therapy is not feasible. Adult dose for ZAVESCA ≥18yrs: 100mg 3 times daily; may reduce to 100mg once or twice daily if diarrhea or tremor occurs. Mild renal impairment (CrCl 50–70mL/min): 100mg twice daily. Moderate renal impairment (CrCl 30–50mL/min): 100mg once daily. Severe renal impairment: not recommended. Children's dosing for ZAVESCA <18yrs: not recommended. Contraindications for ZAVESCA Pregnancy (Cat.X). Warnings/Precautions for ZAVESCA Perform neurological evaluations at baseline, then periodically at 6-month intervals. Reevaluate and consider discontinuation if signs/symptoms of peripheral neuropathy develop (eg, numbness, tingling). GI disease (eg, inflammatory bowel). Use effective methods of contraception during therapy; men should maintain contraception for 3 months after treatment. Elderly. Labor & delivery. Nursing mothers: not recommended. Interactions for ZAVESCA May antagonize imiglucerase. Adverse Reactions for ZAVESCA Diarrhea, weight loss, tremor, flatulence, abdominal pain, GI disturbances, weakness, headache, dizziness, paresthesia, cramps, thrombocytopenia, reduced spermatogenesis, peripheral neuropathy. How is ZAVESCA supplied? Caps—18, 90 Related Disease: Gaucher disease zavesca(Miglustat)治疗高雪病的首个药物 美格鲁特(Miglustat)胶囊剂以商品名zavesca 于2003年7月获得美国FDA批准，由美国ACTELION  PHARMS公司研制，治疗因葡萄糖酶脑苷脂酶活性降低所引起的Ⅰ型戈谢氏病的药物。 戈谢氏病为一种罕见遗传病，由于葡萄糖酶脑苷脂酶活性降低所致。此酶在人体内参与鞘糖脂葡萄糖鞘脑苷鞘氨醇的降解过程，当鞘糖脂葡萄糖鞘脑苷鞘氨醇的降解受到阻碍时，会使富含此种物质的巨嗜细胞的溶酶体在体内蓄积，发生广泛的病理反应，包括严重贫血、血小板减少、肝脾肿大、骨坏死和骨质减少。在治疗上常采用酶替代方法，美格鲁特用于无法以酶替代治疗的成年患者。 药理药效：美格鲁特可降低鞘内糖脂的生物合成率，将葡萄糖苷鞘酶在人体内的浓度降至一个低水平，有助于改善Ⅰ型戈谢氏病患者的肝、脾脏肿大，血色素、血小板计数低下的水平。 使用方法：推荐剂量为1次100mg，1日3次，若患者出现腹泻和震颤等不良反应，剂量可减少为1日1～2次；对轻度肾脏功能受损者(肌酐清除率为50～70ml/min  /1.73m2)推荐剂量为1次100mg，1日2次；对轻度肾脏功能受损者(肌酐清除率为50～70ml/min  /1.73m2)推荐剂量为1次100mg，1日2次；对中度肾脏功能受损者(肌酐清除率为30～50ml/min /1.73m2)推荐剂量为1次100mg，1日1次；对重度肾脏功能受损者不宜应用。 副作用：服药初始的第1个月，常见有震颤、腹泻、胃肠道不适、视力损害、体重减轻、麻木、疼痛、背痛、疲乏、手足烧灼感、肢体沉重、血小板减少等不良反应；对男性有可能影响精子的质量，因此在用药期间尽可能地采取避孕措施，对女性患者在服用期间建议不要怀孕。 美格鲁特胶囊剂的规格为每粒100mg，每盒20粒。  Miglustat (Zavesca®) Miglustat (Zavesca®) is a low-molecular-weight inhibitor of glucosylceramide synthase and α-glucosidase. Zavesca® (100 mg miglustat) is indicated for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease, and may only be used in those patients for whom enzyme replacement therapy is unsuitable. It is approved for this indication in 37 countries including the US and EU since 2003. Zavesca® is also approved in the EU for the treatment of progressive neurological manifestations in adult and pediatric patients with Niemann-Pick type C disease. Miglustat in type 1 Gaucher disease Current status The MAINTENANCE trial is evaluating the long-term safety and efficacy of miglustat as maintenance therapy after a switch from enzyme replacement therapy (ERT) in mild-to-moderate adult type 1 Gaucher disease patients with stable disease. Enrollment in the MAINTENANCE trial was completed during the second quarter of 2008. Results of this study are expected to become available in 2010. Available clinical data Zavesca® (miglustat) 100 mg is the only oral drug available for the treatment of type 1 Gaucher disease, and was approved on the basis of three international open-label clinical trials. The rationale for the use of miglustat in type 1 Gaucher disease is to help balance the overall level of glucosylceramide by reducing its production to a level compatible with breakdown by residual glucocerebrosidase activity, a unique mode of action known as "substrate reduction therapy". Bone manifestations of type 1 Gaucher disease were evaluated in three open-label clinical studies in patients treated with miglustat 100 mg t.i.d. for up to two years (n = 72). In a pooled analysis of uncontrolled data, bone mineral density Z-scores at the lumbar spine and femoral neck increased by more than 0.1 units from baseline in 27 (57%) and 28 (65%) of the patients with longitudinal bone density measurements. There were no events of bone crisis, avascular necrosis or fracture during the treatment period. Milestones 2008 – EU approval for a type II variation for miglustat and bone disease in type 1 Gaucher disease 2008 – Zavesca® launched in Turkey and Brazil 2007 – Zavesca® approved in Australia 2005 – Zavesca® launched in Canada 2004 – Zavesca® launched in the US and Switzerland 2003 – Zavesca® launched in the EU 2002 – Zavesca® in-licensed; marketing authorization granted by European Commission Key scientific literature Pastores G.M. et al. Effect of miglustat on bone disease in adult patients with type 1 Gaucher disease: a pooled analysis of three multinational Open-label studies. Clinical Therapeutics. 29: 1645-53; 2007. Elstein D. et al. Oral maintenance clinical trial with miglustat for type 1 Gaucher disease: switch from or combination with intravenous enzyme replacement. Blood. 110: 2296-2301; 2007. Giraldo P. et al. Short-term effect of miglustat in every day clinical use in treatment-naïve or previously treated patients with type 1 Gaucher’s disease. Haematologica. 91:125-8; 2006. Elstein D. et al. Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type 1 Gaucher disease.. J Inherit Metab Dis 27: 757-66; 2004.