CHENODAL®是FDA批准的合成胆汁酸，于1983年针对患有胆囊结石的患者进行了选择性手术，除了由于全身性疾病或年龄引起的手术风险增加外，其他患者将进行选择性手术.从那时起，护理方面的进步极大地限制了CHENODAL®在这些患者中的使用。
最近，美国食品和药物管理局指出，CHENODAL®在治疗脑卒中黄瘤病（CTX）方面具有医学必要性，CTX是一种罕见的，进行性的，未被诊断的遗传性疾病，影响身体的许多部位.
在CTX患者中，身体是无法正确分解胆固醇，导致毒素（如胆汁甾醇和胆汁醇）随着时间的推移在整个身体内积聚，这可能导致严重的健康问题.
我们目前正采取必要措施增加CTX指征有关CHENODAL®的完整处方信息，该药物具有FDA批准用于治疗CTX的孤儿药物。
对于许多胆结石患者，CHENODAL不是一种合适的治疗方法，应该留给精心挑选的患者，治疗必须伴有系统的肝功能监测。
CHENODAL®禁用于已知的肝细胞功能障碍或胆管异常，如肝内胆汁淤积，原发性胆汁性肝硬化或硬化性胆管炎（见警告）;经过两次连续单次染色后，胆囊被确认为非可视化;不透射线的石头;或胆结石并发症或胆囊手术的令人信服的原因，包括不懈的急性胆囊炎，胆管炎，胆道梗阻，胆石性胰腺炎或胆道胃肠瘘.
CHENODAL®可引起严重的副作用或潜在的并发症，包括肝损伤（肝毒性）和严重的肝病，这可能是致命的。与CHENODAL®相关的不良反应包括胆囊切除率增加，剂量相关性腹泻，血清总胆固醇和低密度脂蛋白增加，以及白细胞计数减少.
CHENODAL®(chenodiol) Tablet, Film Coated
SPL UNCLASSIFIED SECTION
CHENODAL® (CHENODIOL TABLETS) 250 MG
DESCRIPTION
Chenodiol is the non-proprietary name for chenodeoxycholic acid, a naturally occurring human bile acid. It is a bitter-tasting white powder consisting of crystalline and amorphous particles freely soluble in methanol, acetone and acetic acid and practically insoluble in water. Its chemical name is 3α, 7α-dihydroxy-5β-cholan-24-oic acid (C24H40O4), it has a molecular weight of 392.58, and its structure is shown below;
Its chemical name is 3α, 7α-dihydroxy-5β-cholan-24-oic acid (C24H40O4), it has a molecular weight of 392.58, and its structure is shown below;
Chenodiol film-coated tablets for oral administration contain 250 mg of chenodiol.
Inactive ingredients: pregelatinized starch; silicon dioxide; microcrystalline cellulose, sodium starch glycollate; and magnesium stearate; the thin-film coating contains: opadry YS-2-7035 [consisting of methylcellulose and glycerin] and sodium lauryl sulfate
CLINICAL PHARMACOLOGY
At therapeutic doses, chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral cholecystography. Chenodiol has no effect on radiopaque (calcified) gallstones or on radiolucent bile pigment stones.
Chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted in bile. Owing to 60 % to 80% first-pass hepatic clearance, the body pool of chenodiol resides mainly in the enterohepatic circulation; serum and urinary bile acid levels are not significantly affected during chenodiol therapy.
At steady-state, an amount of chenodiol near the daily dose escapes to the colon and is converted by bacterial action to lithocholic acid. About 80% of the lithocholate is excreted in the feces; the remainder is absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates. During chenodiol therapy there is only a minor increase in biliary lithocholate, while fecal bile acids are increased three- to fourfold.
Chenodiol is unequivocally hepatotoxic in many animal species, including sub-human primates at doses close to the human dose. Although the theoretical cause is the metabolite, lithocholic acid, an established hepatotoxin, and man has an efficient mechanism for sulfa |
