药品详细
Pomalidomide(Pomalidomide)
化学结构式图
中文名
Pomalidomide
英文名
Pomalidomide
分子式
C13H11N3O4
化学名
4-amino-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
分子量
Average: 273.2441
Monoisotopic: 273.074955855
Monoisotopic: 273.074955855
CAS号
19171-19-8
ATC分类
L04A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍
Pomalidomide, an analogue of thalidomide, is an immunomodulatory antineoplastic agent. FDA approved on February 8, 2013.
生产厂家
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference |
|
剂型
规格
化合物类型
| Type | small molecule |
| Classes | Not Available |
| Substructures | Not Available |
适应症
药理
| Indication | Pomalidomide is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. |
| Pharmacodynamics | Pomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times). |
| Mechanism of action | Promalidomide is an immunomodulatory agent with antineoplastic activity. It is shown to inhibit the proliferation and induce apoptosis of various tumour cells. Furthermore, promalidomide enhances T cell and natural killer (NK) cell-mediated immunity and inhibited the production of pro-inflammatory cytokines, like TNF-alpha or IL-6, by monocytes. The primary target of promalidomide is thought to be the protein cereblon. It binds to this target and inhibits ubiquitin ligase activity. It is also a transcriptional inhibitor of COX2. |
| Absorption | Pomalidomide is generally well absorbed. The major circulating component is the parent compound. Tmax, single oral dose = 2 -3 hours. When 4 mg of promalidomide is given to patients with multiple myeloma, the steady-state pharmacokinetic parameters are as follows: AUC(T) = 400 ng.hr/mL; Cmax = 75 ng/mL. Promalidomide accumulates following multiple doses. |
| Volume of distribution | Mean apparent volume of distribution (Vd/F), steady-state = 62 – 138 L |
| Protein binding | 12-44% protein bound. It is not concentration dependent. |
| Metabolism |
Promalidomide is hepatically metabolized by CYP1A2 and CYP3A4. The metabolites are 26-fold less active than the parent compound. Minor contributions from CYP2C19 and CYP2D6 have been observed in vitro.
|
| Route of elimination | When a single oral dose (2mg) is given to healthy subjects, 73% of the dose was eliminated in urine. 15% of the dose was eliminated in feces. 2% and 8% of the dose eliminated unchanged as pomalidomide in urine and feces, respectively. |
| Half life | Healthy subjects = 9.4 hours; Multiple myeloma patients = 7.5 hours. |
| Clearance | Total body clearance = 7-10 L/hour |
| Toxicity | Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain and pyrexia. |
| Affected organisms |
|
| Pathways | Not Available |
理化性质
| Properties | |||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Predicted Properties |
|
||||||||||||||||||||||||||||||||||||||||||
药物相互作用
| Drug | Interaction |
|---|---|
| Ketoconazole | Strong CYP3A4 inhibitors may increase levels of pomalidomide. Concomitant therapy should be avoided. |
| Rifampin | Strong CYP3A4 inducers may decrease levels of pomalidomide. Concomitant therapy should be avoided. |
食物相互作用
Not Available
收藏