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药品详细

Pemetrexed(培美曲塞)

化学结构式图
中文名
培美曲塞
英文名
Pemetrexed
分子式
C20H21N5O6
化学名
(2R)-2-{[4-(2-{2-amino-4-oxo-1H,4H,7H-pyrrolo[2,3-d]pyrimidin-5-yl}ethyl)phenyl]formamido}pentanedioic acid
分子量
Average: 427.4106
Monoisotopic: 427.149183429
CAS号
150399-23-8
ATC分类
L01B 抗代谢药
药物类型
small molecule
阶段
approved
商品名
Alimta;
同义名
LY231514;Pemetrexed Disodium;
基本介绍

Pemetrexed (brand name Alimta®) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma as well as non-small cell lung cancer.

生产厂家
  • Eli lilly and co
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Rollins KD, Lindley C: Pemetrexed: a multitargeted antifolate. Clin Ther. 2005 Sep;27(9):1343-82. Pubmed
  2. Lansiaux A, Lokiec F: [Pemetrexed: from preclinic to clinic] Bull Cancer. 2007;94 Spec No Actualites:S134-8. Pubmed
  3. Fuld AD, Dragnev KH, Rigas JR: Pemetrexed in advanced non-small-cell lung cancer. Expert Opin Pharmacother. 2010 Jun;11(8):1387-402. Pubmed
  4. Adjei AA: Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther. 2003 Apr;3(2):145-56. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Pterins
  • Keto-Acids
  • Amino Acids
Substructures
  • Pterins
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Pyrroles
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Keto-Acids
  • Carboxamides and Derivatives
  • Amino Acids
  • Benzoyl Derivatives
  • Cyanamides
  • Benzamides
适应症
Cancer 癌症;
药理
Indication Used in combination with cisplatin for the treatment of malignant pleural mesothelioma in adults whose disease is unresectable or who otherwise are not candidates for potentially curative surgery. Also used as a monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy
Pharmacodynamics Preclinical studies have shown that pemetrexed inhibits the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052). Studies with the MSTO-211H mesothelioma cell line showed synergistic effects when pemetrexed was combined concurrently with cisplatin.
Mechanism of action Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Absorption Not Available
Volume of distribution
  • 16.1 L
Protein binding 81%
Metabolism
Metabolized by Cytochrome P450 Enzymes
Route of elimination Pemetrexed is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration.
Half life 3.5 hours
Clearance
  • 91.8 mL/min [Cancer patients with normal renal function receiving 0.2 to 838 mg/m2 infusion over a 10-minute period]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP -1.5 Not Available
Predicted Properties
Property Value Source
water solubility 4.55e-02 g/l ALOGPS
logP 0.11 ALOGPS
logP 0.73 ChemAxon
logS -4 ALOGPS
pKa (strongest acidic) 3.34 ChemAxon
pKa (strongest basic) 0.96 ChemAxon
physiological charge -2 ChemAxon
hydrogen acceptor count 9 ChemAxon
hydrogen donor count 6 ChemAxon
polar surface area 186.97 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 109.45 ChemAxon
polarizability 43.04 ChemAxon
药物相互作用
Drug Interaction
Ketoprofen The NSAID, ketoprofen, may increase increase the serum concentration of pemetrexed by decreasing its renal clearance. Patients with mild to moderate renal insufficiency (CrCl 45-79 ml/min) should avoid use of ketoprofen within 2 days of a pemetrexed dose. Patients with better renal function do not appear to be at risk. Monitor for toxicity in all patients during concomitant therapy.
Sulindac The NSAID, sulindac, may increase the serum concentration of pemetrexed by decreasing its elimination. This interaction more prevalent in patients with mild to moderate renal insufficiency. Consider alternate therapy or monitor for pemetrexed toxicity during concomitant therapy.
Tiaprofenic acid Tiaprofenic acid may decrease Pemetrexed excretion. Tiaprofenic acid should not be used around the time when Pemetrexed is administered.
Tolmetin Tolmetin may decrease the renal excretion of Pemetrexed in patients with decreased creatinine clearance. Tolmetin may be withheld in these patients from 2 days before to 2 days after Pemetrexed administration.
食物相互作用
Not Available

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