Topiramate

Topiramate 속성

Topiramate MSDS

RWJ-17021

Topiramate C화학적 특성, 용도, 생산

개요

Topiramate, a novel sulfamate-substituted D-fructose derivative, was launched in the United Kingdom as an adjunct therapy for use in partial seizures with or without secondary generalized seizures in adult patients inadequately controlled on conventional antiepileptics. Topiramate is structurally distinct from other available antiepileptics and functions through a unique combination of several mechanisms. It appears to act by blocking voltage-sensitive sodium channels to raise the action potential threshold and block the spread of seizure, enhancing GABA activity at postsynaptic GABA receptors and reducing glutamate activity at postsynaptic AMPAtype receptors, and is also a carbonic anhydrase inhibitor. Topiramate is orally active with rapid absorption, high bioavailability, and long duration of action. Excellent efficacy has been reported as an add-on therapy in epilepsy and it is also being evaluated as a monotherapy.

화학적 성질

White-to-Off-White Crystalline Powder

용도

Topiramate may be used as a pharmaceutical reference standard for the quantification of the analyte in pharmaceutical formulations using high-performance liquid chromatography technique and spectrophotometric technique.

정의

ChEBI: A hexose derivative that is 2,3:4,5-di-O-isopropylidene-beta-D-fructopyranose in which the hydroxy group has been converted to the corresponding sulfamate ester. It blocks voltage-dependent sodium channe s and is used as an antiepileptic and for the prevention of migraine.

Biological Functions

Topiramate is most useful in patients with generalized tonic–clonic seizures and those with partial complex seizures. Topiramate causes a higher incidence of CNSrelated side effects (primarily cognitive slowing and confusion) than other AEDs. It does not appear to cause a significant incidence of rashes or other hypersensitivity reactions; however, a significantly higher incidence of kidney stones has been observed in persons receiving topiramate than in a similar untreated population.

일반 설명

TPM is a sulphamate-substituted monosaccharide, a derivativeof the naturally occurring sugar D-fructose thatexhibits broad and potent AED actions at both glutamateand GABA receptors.19 It has good oral bioavailability of85% to 95%, most likely resulting from its structural similarityto D-glucose. Thus, it may be actively transportedinto the brain by the D-glucose transporter. (Recall thatD-fructose and D-glucose have identical stereochemistry atmany of their chiral centers.) Only about 20% of the drugis eliminated by hepatic metabolism (CYP2C19), the remainingdrug is excreted unchanged by the kidneys.57 Thesulphamate ester is hydrolyzed by sulfatases to the correspondingprimary alcohol, which is further oxidized to thecorresponding carboxylic acid. Even though there are noreports of significant interactions between TPM and otherAEDs, TPM is said to have a weak carbonic anhydrase inhibitoryactivity because of the presence of the sulphamatemoiety. Thus, concomitant use of TPM with other carbonicanhydrase inhibitors should be avoided.57 The exact mechanismof actions are still unknown, but TPM appears toblock glutamate release, antagonize glutamate kainicacid/AMPA receptors, and increase GABAergic transmissionby binding to a site distinct from BZDs or barbiturateson the GABAA receptor complex.

생물학적 활성

Anticonvulsant. Antagonizes GluR5 kainate receptors (IC 50 = 0.46 μ M), acts as a positive allosteric modulator of GABA A receptor-mediated currents, inhibits Na v channels (IC 50 = 48.9 μ M) and inhibits L-type Ca 2+ channels. Also inhibits carbonic anhydrase (CA) (K i values are 0.1 and 0.2 μ M at rat CA II and CA IV respectively), which lowers intracellular neuronal pH.

Mechanism of action

The mechanism of action for topiramate is unknown, but several actions are thought to contribute to its AED activity. It blocks repetitive firing by acting on sodium channels, may enhance GABAA-mediated chloride flux, and appears to be an antagonist at the AMPA and KA receptors, thus blocking the effect of glutamate. In addition, recent evidence suggests inhibition of L-type calcium currents.

Pharmacokinetics

Topiramate is rapidly absorbed, with at least an 80 to 95% oral bioavailability that is unaffected by food. Following an oral dose of topiramate, peak plasma concentration is reached in 1 to 4 hours, exhibiting linear pharmacokinetics. Protein binding is minimal (<20%), and the usual elimination half-life is 20 to 30 hours, allowing a twice-daily dosing regimen. In the absence of enzyme-inducing drugs, approximately 70 to 80% of the drug is excreted unchanged in the urine, with the remainder as metabolites resulting from oxidation and hydrolysis. Enzyme-inducing AEDs alter the pharmacokinetics of topiramate by reducing its plasma levels and increasing its rate of elimination.
In children from 4 to 17 years of age, topiramate exhibits linear pharmacokinetics, with a 50% increase in clearance rate compared to adults. Topiramate may require up to a 50% dose reduction in patients with renal insufficiency, and a replacement dose may be needed after renal dialysis. Topiramate has demonstrated teratogenicity in animal studies.

Clinical Use

Topiramate is a sulfamate-substituted monosaccharide derived from fructose with a broad spectrum of AED activity. It is approved for monotherapy or as an adjunct drug for partial or primary generalized tonic-clonic seizures in patients older than 10 years, as adjunct therapy in children aged from 2 to 10 years with partial-onset seizures, and in persons older than 2 years with Lennox-Gastaut syndrome. Topiramate also is approved for the prophylaxis of migraine headaches.

부작용

Common CNS side effects associated with topiramate therapy include drowsiness, dizziness, impaired concentration and memory, speech and language difficulties, and confusion. These effects develop during the first weeks of therapy and may decline over time. Acute closed-angle glaucoma caused by topiramate requires immediate evaluation. Only rare hepatic or bone marrow effects have been noted thus far; however, an increased incidence of renal stones is troublesome and probably related to the drug's activity as a carbonic anhydrase inhibitor, reducing citrate excretion and increasing urinary pH. Use of additional carbonic anhydrase inhibitors, a ketogenic diet, or a family history of nephrolithiasis may be considered as contraindications for using topiramate.
Topiramate is not devoid of potential interaction properties: It induces CYP3A4 and inhibits CYP2C19, thus significantly increasing plasma phenytoin levels. Topiramate also may decrease the effectiveness of oral contraceptives.

Topiramate 준비 용품 및 원자재

원자재

준비 용품

Topiramate 공급 업체

공급자	전화	이메일	국가	제품 수	이점
Huadong Medicine (Xi'an)Bodyguard Pharmaceutical Co.,Ltd.	+86-029-86185165 +8618629664246	guoyuan@eastchinapharm.com	China	1615	58
Hebei Mojin Biotechnology Co., Ltd	+8613288715578	sales@hbmojin.com	China	12456	58
Hebei Yanxi Chemical Co., Ltd.	+8617531190177	peter@yan-xi.com	China	5993	58
Xiamen Wonderful Bio Technology Co., Ltd.	+8613043004613	Sara@xmwonderfulbio.com	China	305	58
Guangzhou Tengyue Chemical Co., Ltd.	+86-86-18148706580 +8618826483838	evan@tyvovo.com	China	152	58
Sigma Audley	+86-18336680971 +86-18126314766	nova@sh-teruiop.com	China	525	58
Ouhuang Engineering Materials (Hubei) Co., Ltd	+8617702722807	admin@hbouhuang.com	China	2259	58
Shanghai Daken Advanced Materials Co.,Ltd	+86-371-66670886	info@dakenam.com	China	15928	58
Henan Tianfu Chemical Co.,Ltd.	+86-0371-55170693 +86-19937530512	info@tianfuchem.com	China	21691	55
Nanjing ChemLin Chemical Industry Co., Ltd.	025-83697070	product@chemlin.com.cn	CHINA	3012	60

Topiramate 관련 검색: