Eliglustat (brand name CERDELGA) is a glucosylceramide synthase inhibitor used in the treatment of Gaucher disease (GD). Eliglustat is indicated for the long-term treatment of adult individuals with Gaucher disease type 1 (GD1) who are CYP2D6 normal metabolizers, intermediate metabolizers, or poor metabolizers as detected by an FDA-cleared test (1). Gaucher disease is an autosomal recessive metabolic disorder characterized by accumulation of glucosylceramide (a sphingolipid also known as glucocerebroside) within lysosomes. This is caused by a malfunction of the enzyme acid beta-glucosidase, encoded by the gene GBA. Type 1 GD may present in childhood or adulthood with symptoms including bone disease, hepatosplenomegaly, thrombocytopenia, anemia and lung disease and –– unlike Gaucher types 2 and 3 –– does not directly affect the central nervous system primarily (2). Eliglustat, a ceramide mimic, inhibits the enzyme that synthesizes glucosylceramides (UDP-Glucose Ceramide Glucosyltransferase), thereby reducing the accumulation of these lipids in the lysosome (3). Eliglustat is broken down to inactive metabolites by CYP2D6 and, to a lesser extent, CYP3A (3). The dosage of eliglustat is based on the individual’s CYP2D6 metabolizer status. Individuals with normal CYP2D6 activity are termed normal metabolizers (NM), those with reduced activity are termed intermediate metabolizers (IM), and if activity is absent, poor metabolizers (PM). The FDA-approved drug label for eliglustat provides specific dosage guidelines based on their CYP2D6 status and concomitant usage of CYP2D6 or CYP3A inhibitors, and states that hepatic and renal function should also be considered when determining the appropriate dosage (Table 1). The label also states that CYP2D6 ultrarapid metabolizers (UM) may not achieve adequate concentrations of eliglustat for a therapeutic effect, and that for individuals for whom a CYP2D6 genotype cannot be determined, a specific dosage cannot be recommended (1). Dosing recommendations for eliglustat have also been published by the Dutch Pharmacogenetics Working Group (DPWG) based on CYP2D6 metabolizer type (Table 2) and include dose adjustments for dosing eliglustat with medications that alter CYP2D6 and or CYP3A function (Table 3).
依利格鲁司他（商品名：CERDELGA）是一种葡萄糖神经酰胺合酶抑制剂，用于治疗戈谢病（GD）。依利格鲁司他适用于经美国食品药品监督管理局（FDA）批准的检测方法检测为CYP2D6正常代谢者、中间代谢者或慢代谢者的1型戈谢病（GD1）成年患者的长期治疗（1）。戈谢病是一种常染色体隐性代谢紊乱疾病，其特征是溶酶体内葡萄糖神经酰胺（一种鞘脂，也称为葡萄糖脑苷脂）的蓄积。这是由基因GBA编码的酸性β - 葡萄糖苷酶功能异常引起的。1型戈谢病可在儿童期或成年期出现，症状包括骨骼疾病、肝脾肿大、血小板减少、贫血和肺部疾病，并且——与2型和3型戈谢病不同——主要不直接影响中枢神经系统（2）。依利格鲁司他是一种神经酰胺类似物，可抑制合成葡萄糖神经酰胺的酶（UDP - 葡萄糖神经酰胺葡萄糖基转移酶），从而减少这些脂质在溶酶体中的蓄积（3）。依利格鲁司他被CYP2D6分解为无活性的代谢产物，在较小程度上也被CYP3A分解（3）。依利格鲁司他的剂量基于个体的CYP2D6代谢状态。CYP2D6活性正常的个体被称为正常代谢者（NM），活性降低的个体被称为中间代谢者（IM），如果没有活性，则为慢代谢者（PM）。FDA批准的依利格鲁司他药品标签根据其CYP2D6状态和CYP2D6或CYP3A抑制剂的联合使用情况提供了具体的剂量指南，并指出在确定合适剂量时还应考虑肝肾功能（表1）。该标签还指出，CYP2D6超快代谢者（UM）可能无法达到产生治疗效果所需的依利格鲁司他浓度，对于无法确定CYP2D6基因型的个体，无法推荐具体剂量（1）。荷兰药物基因组学工作组（DPWG）也根据CYP2D6代谢类型发布了依利格鲁司他的给药建议（表2），并包括与改变CYP2D6和/或CYP3A功能的药物联合使用依利格鲁司他时的剂量调整（表3）。
