グアンファシン塩酸塩 化学特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結晶
効能
血圧降下薬, α2アドレナリン受容体作動薬
商品名
インチュニブ (塩野義製薬)
使用
Centrally acting a-adrenoceptor agonist. Antihypertensive
一般的な説明
Guanfacine hydrochloride,N-(aminoiminomethyl)-2,6-dichlorobenzeneacetamide(Tenex), is structurally related to clonidine hydrochloride andguanabenz acetate and shares many of their pharmacologicalproperties. The drug has a longer duration of action than eitherclonidine hydrochloride or guanabenz acetate. It lasts upto 24 hours. It also requires much longer (8–12 hours) for apeak effect to occur after the drug is administered.
生物活性
Selective α 2A -adrenoceptor agonist (K d = 31 nM). Displays 60-fold selectivity over α 2B -adrenoceptors. Also available as part of the α 2 -Adrenoceptor Tocriset™ .
薬物動態学
The pharmacokinetic properties for guanfacine differ from those of clonidine, guanabenz, and α-methyldopa. At pH 7.4,
guanfacine is predominately (67%) in the nonionized, lipid-soluble base form, which accounts for its high oral
bioavailability (>80%). Following an oral dose, peak plasma concentrations occur in 1 to 4 hours, with a relatively long
elimination half-life of 14 to 23 hours. The maximum blood pressure response occurs in 8 to 12 hours after oral
administration and is maintained up to 36 hours following its discontinuation. Following IV dosing, guanfacine achieves
the highest concentrations in liver and kidney, with low concentrations in the brain. Guanfacine is 64% bound to
plasma proteins. In patients with hepatic or renal impairment, its elimination half-life may be prolonged.
Guanfacine is metabolized principally by hepatic hydroxylation to its inactive metabolite, 3-hydroxyguanfacine (20%),
which is eliminated in the urine as its glucuronide (30%), sulfate (8%), or mercapturic acid conjugate (10%), and 24 to
37% is excreted as unchanged guanfacine. Its nearly complete bioavailability suggests no evidence of any
first-pass effect. Guanfacine and its inactive metabolites are excreted principally in urine, with approximately 80% of its
oral dose excreted in urine within 48 hours.
臨床応用
Overall, the therapeutic applications for guanfacine are similar to those of the other centrally acting α2-adrenergic
agonists and methyldopa. It has been effective as monotherapy in the treatment of patients with mild to moderate
hypertension. One advantage for guanfacine is its once-a-day dosing schedule. The use of diuretics to prevent
accumulation of fluid may allow a reduction in the dosage for guanfacine.
副作用
Overall, although the frequency of troublesome adverse effects produced by guanfacine is similar to that produced by
clonidine and the other centrally acting sympatholytics, their incidence and severity are lower with guanfacine. Unlike
clonidine, abrupt discontinuation of guanfacine rarely results in rebound hypertension. When a withdrawal syndrome
has occurred, its onset was slower and its symptoms less severe than the syndrome observed with clonidine.
グアンファシン塩酸塩 上流と下流の製品情報
原材料
準備製品