【药物名称】bexarotene
【分子式成分】4-[1-(5，6，7，8-四氢-3，5，5，8，8-五甲基-2-萘基）乙烯基]苯甲酸

【制剂规格】本品为75mg口服明胶软胶囊制剂。

【药理毒理】由美国Ligand制药公司研制，2000年1月15日在美国首次上市。本品可选择性地结合并激活视黄酸类（retinoid）X受体亚型（RXRα，RXRβ，RXRγ）。RXR可与多种受体[如维A酸受体（RAR）、维生素D受体、甲状腺素受体，以及过氧化物酶体增生物激活受体（PPAR）]形成异二聚体。这些受体一旦被激活可控制基因的表达，控制细胞分化和增生。在体外试验中，本品可抑制某些肿瘤细胞系的生长；在动物模型体内试验中，本品可诱使乳腺瘤消退。本品口服后，约2小时达血浆峰浓度，半衰期约为7小时。含脂食物可增加本品吸收，较之葡萄糖溶液，含脂食物可使300mg本品的AUC及Cmax分别上升35%和48%；本品可与血浆蛋白高度结合（99%）。

在血浆中能测得本品的四种代谢产物：6-和7-羟基bexarotene以及6-和7-氧代bexarotene。体外试验显示细胞色素P450 3A4是对氧化产物形成及氧化产物葡糖醛酸化起主要作用的酶。
经对Ⅱ型糖尿病患者进行本品及本品代谢物肾消除过程的检测，目前认为本品主要大部分随胆汁消除，基本不随尿液排出。
【 临床评价】两项开放性研究显示本品对早期及晚期难治性皮肤T-细胞淋巴瘤有效。
在第一项研究中，对至少两种治疗方法无反应或不能耐受的早期皮肤T-细胞淋巴瘤病人服用本品一日300mg/m2后，28例病人中有15例（54%）获得全部或部分反应（改善至少达50%以上），而更高剂量组反应率为10例/15例（67%），此外，一日300mg/m2组中有2例病人在25周内复发。

在第二项研究中，94例至少一种全身性治疗方法无效的晚期皮肤T-细胞淋巴瘤病人中，56例接受本品一日300mg/m2后有25例（45%）获得反应，另外35例接受较高剂量本品，有21例（55%）获得瓜；低剂量组有反应的病人中有9例经中位时间19周复发。

在两项研究中，共有84例病人接受本品一日300mg/m2，其中3例（4%）获得完全反应，40例（48%）获得部分瓜；在高剂量组中，完全反应率为9例/53例（17%）。

【适 应 证】口服治疗顽固性皮肤T-细胞淋巴瘤的皮肤症状。

【不良反应】本品的多数不良反应与剂量有关，使用本品后大部分病人会出现高甘油三酯血症、高胆固醇血症及高密度脂蛋白水平低下，通常需要对症治疗或减少本品的用药剂量；此外，尚易发生中枢性甲状腺机能减退并需要治疗，还常发生头痛、虚弱、白细胞减少、贫血、感染、皮疹、光敏反应和脱发。临床研究中约30%的病人停药；亦有转氨酶升高、致命性胰腺炎和致命性胆汁郁积的报道。
【用法用量】治疗皮肤T-细胞淋巴瘤的推荐剂量为一日300mg/m2，与食物同服；若8周后尚未见疗效，则可增加剂量至一日400mg/m2，最佳治疗时间目前尚未确定。

【注意事项】本品可对胎儿造成伤害，故孕妇禁用。
在动物试验中本品可致睾丸萎缩。
本品理论上与P450 3A4诱导剂或抑制剂可发生相互作用；已发现经P4503A4代谢的吉非贝齐（gemfibrozil）可升高本品血浆浓度，这至少部分归因于吉非贝剂能抑制细胞色素P4503A4；本品与胰岛素、磺酰脲类、二甲双胍、曹格列奈或噻唑烷二酮（格列酮）类药物合用时可致低血糖。由于本品是一种VA衍生物，与VA合用可增加药物的毒性作用。

对bexarotene或该产品的其他成分过敏者禁用。

TARGRETIN GEL 1% 60GM
Generic Name: BEXAROTENE
Class: R
Manufacture: EISAI INC
Strength: 1%
Size: 1
Unit: EACH
      
TARGRETIN CAP 75MG 100
Generic Name: BEXAROTENE
Class: R
Manufacture: EISAI INC
中文名: 蓓萨罗丁
Strength: 75MG
Size: 100
Unit: CAP

CHEMICAL NAME
BEXAROTENE.

INDICATIONS
Targretin(Bexarotene) is used to treat a certain type of cancer affecting the skin, certain types of blood cells (lymphocytes), and lymph nodes (cutaneous T-cell lymphoma or CTCL).

DIRECTIONS
Take Targretin Capsules by mouth, usually once daily with a meal; or take as directed by your doctor.

The dosage is based on your medical condition and response to therapy. It may take up to several months of continued use to see a response to treatment. Your dosage may need to be adjusted by your physician during this time. Read the patient information leaflet provided by your pharmacist and ask questions if any of the information is unclear.

MISSED DOSE:

If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

SIDE EFFECTS
Headache, rash, nausea, vomiting, dry skin, diarrhea, or trouble sleeping may occur. If any of these effects persist or worsen, notify your doctor.
Tell your doctor immediately if any of these serious side effects occur: unusual fatigue, stomach pain, swelling of thehandsorfeet,musclepain/stiffness/cramps, unusually slow heartbeat.

Tell your doctor immediately if any of these unlikely but serious side effects occur: yellowing eyes and skin, dark urine, vision changes, unusual weight loss.
This medication can lower the body's ability to fight an infection. Notify your doctor promptly if you develop any signs of an infection such as fever, chills, or persistent sore throat. If you notice other effects not listed above, contact your doctor or pharmacist.

PRECAUTIONS
Tell your doctor your medical history, especially of: heart disease, high cholesterol or triglyceride levels, pancreatitis, diabetes, kidney problems, liver problems, thyroid problems (e.g., hypothyroidism), cataracts, allergies. This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, use a sunscreen, and wear protective clothing when outdoors. Because this medication can lower your body's ability to fight an infection, do not touch your eyes or the inside of your nose without first washing your hands. Donothaveimmunizations/vaccinations without the consent of your doctor and avoid contact with people who have recently received oral polio vaccine. This medication must not be used during pregnancy. If you become pregnant or think you may be pregnant, informyourdoctorimmediately. Two effective forms of birth control (see Warning section for a complete list of appropriate birth control) must be used for 1 month before starting this drug, during the use of this drug, and for 1 month after stopping this drug. It is not known if this drug passes into breast milk. Due to the potential risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding. It is recommended men use condoms during sexual activity while on this medication and for 1 month after the last dose.

OVERDOSAGE
If overdose is suspected, contact your local poison control center or emergency room immediately.

INFORMATION
Do not share this medication with others. Store at room temperature between 36 and 86 degrees F (2 to 30 degrees C) away from light and moisture.

NOTES
The above information is intended to supplement, not substitute for, the expertise and judgment of your physician,pharmacist, or other healthcare professional. It should not be construed to indicate that the use of the product issafe,appropriate, or effective for you. Consult yourhealthcare professional before taking the product.

DRUG INTERACTIONS
Bexarotene is not recommended for use with gemfibrozil.Ifyouaretakinggemfibrozil, your treatment may be changed to a different cholesterol/lipid-lowering drug. Ask your doctor or pharmacist for more details. Tell your doctor of all prescription and nonprescription medication you may use, especially of: macrolide antibiotics (e.g., clarithromycin, erythromycin), cimetidine, azole antifungals.(e.g.,itraconazole,ketoconazole),nefazodone,phenytoin,phenobarbital, rifampin, tamoxifen. This medication may decrease theeffectiveness of combination-type birth control pills. This can result in pregnancy. You will need to use additional form(s) of reliable birth control while using this medication (see Warning section for a complete list of appropriate birth control). Consult your doctor or pharmacist for details. Do not eat grapefruit or drink grapefruit juice unless your doctor instructs you otherwise. This medication can affect the results of certain lab tests.
Make sure laboratory personnel and your doctors know you use this drug. Do not start or stop any medicine without doctor or pharmacist approval.

      
新合成的视黄醇有希望治疗银屑病
以前的研究表明，bexarotene可以有效对抗皮肤T细胞淋巴瘤，但在此以前，一直没人检测它用于良性、高增生性疾病如银屑病的效果。
在这项预试验中，荷兰Nijmegen大学医疗中心的史密特(Jurgen V. Smit)和同事评估了29名脂斑型银屑病人的后果，这些病人用bexarotene(直到3.0/kg/天)治疗了12周。治疗前、后对活组织样本进行了免疫组织化学分析。
结果揭示，bexarotene对增生、炎症和分化参数都有显著效果。除对增生标志物Ki-67的作用以外，其它没有明显的剂量反应关系。
“还需要对更多病人研究更高剂量的bexarotene，以确定这种新型视黄醛可能的剂量相关性免疫组织化学作用，并阐明RXR在视黄醛有关的角蛋白表达中的信号作用”。