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药品详细

Topiramate(托吡酯)

化学结构式图
中文名
托吡酯
英文名
Topiramate
分子式
C12H21NO8S
化学名
[(1R,2S,6S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.0^{2,6}]dodecan-6-yl]methyl sulfamate
分子量
Average: 339.362
Monoisotopic: 339.098787343
CAS号
97240-79-4
ATC分类
N03A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Topiramate (brand name Topamax) is an anticonvulsant drug produced by Ortho-McNeil Neurologics, a division of Johnson & Johnson. It is used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). It is also Food and Drug Administration (FDA) approved for, and now most frequently prescribed for, the prevention of migraines. [Wikipedia]. A combination product containing phentermine + topiramate extended-release called QSYMIA® is indicated for the management of obesity.

生产厂家
  • Accord healthcare inc
  • Apotex inc etobicoke site
  • Aurobindo pharma ltd
  • Barr laboratories inc
  • Cipla ltd
  • Glenmark generics ltd
  • Invagen pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Ortho mcneil janssen pharmaceuticals inc
  • Pliva hrvatska doo
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Torrent pharmaceuticals ltd
  • Unichem laboratories ltd
  • Upsher smith laboratories inc
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Blum D, Meador K, Biton V, Fakhoury T, Shneker B, Chung S, Mills K, Hammer A, Isojarvi J: Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy. Neurology. 2006 Aug 8;67(3):400-6. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Carbohydrates
Substructures
  • Glycerol and Derivatives
  • Pyrans
  • Acetals and Derivatives
  • Sulfuric Acids and Derivatives
  • Sulfonyls
  • Carbohydrates
  • Ethers
  • Dioxoles
  • Heterocyclic compounds
适应症
药理
Indication Used for the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures and also for the prevention of migraine headaches. In children it is also used for treatment of Lennox-Gastaut syndrome. Qsymia® is indicated for the treatment and management of obesity.
Pharmacodynamics Topiramate is an anticonvulsant indicated in the treatment of epilepsy and migraine. Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. There is evidence that topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particular subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secundarily generalized tonic-clonic seizures in the kindling model, findings predective of a broad spectrum of antiseizure activities clinically.
Mechanism of action The precise mechanism of action of topiramate is not known. However, studies have shown that topiramate blocks the action potentials elicited repetitively by a sustained depolarization of the neurons in a time-dependent manner, suggesting a state-dependent sodium channel blocking action. Topiramate also augments the activity of the neurotransmitter gamma-aminobutyrate (GABA) at some subtypes of the GABAA receptor (controls an integral chloride channel), indicating a possible mechanism through potentiation of the activity of GABA. Topiramate also demonstrates antagonism of the AMPA/kainate subtype of the glutamate excitatory amino acid receptor. It also inhibits carbonic anhydrase (particularly isozymes II and IV), but this action is weak and unlikely to be related to its anticonvulsant actions.
Absorption Rapid with pleak plasma concentrations occurring after 2 hours and a bioavailability of 80%.
Volume of distribution Not Available
Protein binding 15-41% (over the blood concentration range of 0.5 - 250 mg/mL).
Metabolism
Not extensively metabolized, 70% of the dose is eliminated unchanged in the urine. The other 30% is metabolized hepatically to six metabolites (formed by hydroxylation, hydrolysis, and glucuronidation), none of which constitute more than 5% of an administered dose.
Route of elimination Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose).
Half life 19 to 23 hours
Clearance
  • Oral plasma cl=20 – 30 mL/min [in humans following oral administration]
Toxicity Symptoms of overdose include abdominal pain, agitation, blurred vision, convulsions, depression, dizziness, double vision, drowsiness, impaired coordination, impaired mental activity, low blood pressure, reduced consciousness, severe diarrhea, sluggishness, and speech problems.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
water solubility 9.8 mg/mL Not Available
logP -0.7 Not Available
Predicted Properties
Property Value Source
water solubility 6.80e+00 g/l ALOGPS
logP 1.29 ALOGPS
logP 0.13 ChemAxon
logS -1.7 ALOGPS
pKa (strongest acidic) 11.09 ChemAxon
pKa (strongest basic) -3.7 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 8 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 115.54 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 72.3 ChemAxon
polarizability 32.42 ChemAxon
药物相互作用
Drug Interaction
Acetazolamide Additive renal carbonic anhydrase inhibition may occur increasing the risk of crystaluria and renal calculi. Increased risk of nephrolithiasis. Consider altnerate therapy.
Brinzolamide As both brinzolamide and topiramate are carbonic anhydrase inhibitors, there is an increased risk of adverse effects.The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Avoid concurrent use of different carbonic anhydrase inhibitors when possible.
Carbamazepine Carbamazepine may decrease the effectiveness of Topiramate by increase its clearance. Monitor for changes in the therapeutic and adverse effects of Topiramate if Carbamazepine is initiated, discontinued or dose changed. Adverse effects related to CNS depression have also been observed during concomitant therapy.
Chlorothiazide Thiazide diuretics such as chlorothiazide may enhance the hypokalemic effect of topiramate. Thiazide diuretics may increase the serum concentration of topiramate. Monitor for increased topiramate concentrations/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary.
Ethinyl Estradiol Topiramate may decrease the effect of the oral contraceptive, Ethinyl estradiol. An alternate form of contraception should be used during concomitant therapy.
Fosphenytoin Increased phenytoin/decreased topiramate
Lithium Topiramate could modify lithium levels
Maraviroc Topiramate, a CYP3A4 inducer, may decrease the serum concentration of Maraviroc by increasing Maraviroc metabolism and clearance. A dose adjustment of Maraviroc may be required. Monitor for changes in Maraviroc therapeutic and adverse effects if Topiramate is initiated, discontinued or dose changed.
Mestranol Topiramate may decrease the effect of the oral contraceptive, Mestranol. An alternate form of contraception should be used during concomitant therapy.
Phenytoin Increased phenytoin/decreased topiramate
Tobramycin Increased risk of nephrotoxicity
Triprolidine The CNS depressants, Triprolidine and Topiramate, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Ulipristal Concomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
食物相互作用
Not Available

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