ゾニサミド 化学特性,用途語,生産方法
外観
白色～うすい黄色、結晶～結晶性粉末
溶解性
エタノール(95)に溶けにくく、水に極めて溶けにくい。
用途
ベンズイソキサゾール構造を 基本骨格にスルファモイル基を有していま す。カルシウム透過性抑制作用を示します。
効能
抗けいれん薬, 抗てんかん薬, パーキンソン病治療薬
商品名
エクセグラン (大日本住友製薬); ゾニサミド (寿製薬); トレリーフ (大日本住友製薬); トレリーフ (大日本住友製薬)
説明
Zonisamide is a broad-spectrum antiepileptic effective in the treatment of refractory
seizures. In cultured spinal cord neurons, zonisamide blocks the sustained firing of action
potentials induced by depolarizing steps of current injected across the membrane.
化学的特性
Off-White Powder
使用
Sulfonamide antiseizure agent; blocks repetitive firing of voltagesensitive sodium channels and reduces voltage-sensitive T-type calcium currents. Heterocyclic methanesulfonide with anticonvulsant pro
perties. The compound is under investigation for potential therapeutic use as an antiepileptic drug. Anticonvulsant.
定義
ChEBI: A 1,2-benzoxazole compound having a sulfamoylmethyl substituent at the 3-position.
生物学の機能
Zonisamide has only recently been approved for use in
the United States, although it has been available in
Japan for several years. It is effective in partial complex
and generalized tonic–clonic seizures and also appears
to be beneficial in certain myoclonic seizures. It has a
long half-life (about 60 hours) and requires about 2
weeks to achieve steady-state levels. It causes cerebellovestibular
side effects similar to those of most
other AEDs sharing its mechanism of action. In addition,
it appears to cause an increased incidence of kidney
stones.
一般的な説明
Zonisamide, a sulfonamide-type anticonvulsant was recentlyapproved for adjunctive therapy in the treatment ofpartial seizures in adults with epilepsy.Zonisamide isprimarily metabolized by reductive ring cleavage of the 1,2-benzisoxazole ring to 2-sulfamoyl-acetyl-phenol. This biotransformation is mainly carried out by theintestinal bacteria rather than the mammalian cytosolicaldehyde oxidase suggested earlier.Again, because ofthe presence of a sulfonamide moiety in zonisamide molecule,precaution should be given to patients who have ahistory of hypersensitivity reactions toward sulfonamidedrugs and concomitant use of zonisamide with other carbonicanhydrase inhibitors should also be avoided.
作用機序
Zonisamide is a sulfonamide derivative that is indicated as an adjunct for partial seizures in patients older than 16 years whose
seizures are not controlled by first-line drugs. In Japan, it is used for myoclonic seizures as well. Apparently, it has more than
one mechanism of action—all as yet unidentified. It is known to produce blockade of both sodium and T-type calcium channels. Because it also affects dopaminergic transmission, bipolar or schizoaffective disorder patients may
improve.
薬物動態学
The absorption for orally administered zonisamide is slow but nearly complete. Its
pharmacokinetics are nonlinear, with a half life of 50 to 70 hours when administered alone or 27 to 46 hours when administered
concurrently with enzyme-inducing AEDs. Protein binding is moderate (<50%). An oral dose of zonisamide is completely
absorbed, with peak plasma concentration occurring in 2 to 6 hours. Although the presence of food will delay the attainment of
its peak plasma concentration, oral bioavailability does not appear to be altered. More than one-third of each oral dose is
excreted in the urine in an unchanged form. The routes of metabolism for zonisamide include acetylation to form its N-acetyl
metabolite, reduction by CYP3A4/CYP2D6, and the formation of an open-ring metabolite, 2-sulfamoylacetyl phenol. These
metabolites subsequently are eliminated unconjugated or glucuronidated in the urine, with an elimination half-life of 63 hours.
Its coadministration with enzyme-inducing AEDs, such as phenytoin, CBZ, or phenobarbital, and with valproate will alter its
pharmacokinetics by reducing its half-life and serum concentration. The half-life for zonisamide is decreased to 27 hours in the
presence of phenytoin, to 38 hours in the presence of either CBZ or phenobarbital, and to 46 hours with valproate. Other drugs
that inhibit or induce CYP3A4 could affect the metabolism of zonisamide.
Zonisamide should be used with caution in patients with hepatic or renal disease. It also has shown to be teratogenic in animal
studies.
副作用
Zonisamide is contraindicated in patients with a history of allergy to sulfonamides. The most frequent side effects include
somnolence, anorexia, dizziness, agitation, confusion, headache, cognitive impairment, and memory loss. In addition, an
incidence of drug-induced psychosis has been noted. Reports from both the United States and Europe have indicated
that development of renal stones may occur with use of this drug. A family history of nephrolithiasis may be a contraindication,
and urinary monitoring for hypercalciuria may be warranted in bedridden patients or those receiving multiple AEDs.
Although the incidence of severe rashes attributable to zonisamide is low, sulfonamides are associated with Stevens-Johnson
syndrome. Thus, it is recommended to discontinue the drug immediately should a rash occur.
安全性プロファイル
Moderately toxic by ingestion,intraperitoneal, subcutaneous, and intravenous routes. Anexperimental teratogen. Other experimental reproductiveeffects. When heated to decomposition it emits very toxicfumes of SOx and NOx. An anticonvulsant.
ゾニサミド 上流と下流の製品情報
原材料
準備製品