シロミラスト 化学特性,用途語,生産方法
効能
喘息治療薬, 抗炎症薬, ホスホジエステラーゼ4阻害薬
化学的特性
Cilomilast is White Solid
使用
Cilomilast is a selective phosphodiesterase 4 (PDE4) inhibitor and can be used in treatment of chronic obstructive pulmonary disease.
作用機序
Cilomilast contains the dialkoxyphenyl ring characteristic of selective PDE4 inhibitors. The ether
oxygens hydrogen bond to a glutamine in the binding pocket, and the cyclopentyl ring adds
additional hydrophobic interactions. The oxygen atoms of the carboxyl group form hydrogen
bonds with water that is coordinated with Mg2+ located in the distal end of the binding pocket.
Orally administered cilomilast is 96% bioavailable. Food does not interfere with the overall
absorption; however, food does slow down the rate. Cilomilast is 99% bound to albumin in the
plasma and is metabolized in the liver by CYP2C8. The metabolism is extensive and results in
oxidation, carboxyl group glucuronidation, and dealkylation of the cyclopentyl group, followed by
glucuronidation or sulfation.
薬物動態学
Cilomilast is rapidly absorbed following oral administration (96% bioavailability), has an elimination half-life of 7 hours, and is
extensively metabolized, but not by cytochrom P450 enzymes. The drug shows considerably more selectivity than roflumilast toward
PDE4D, and this might account for the common side effects of nausea and emesis. Studies regarding the benefits of cilomilast
versus placebo in the treatment of asthma have not been very encouraging, but significant improvement was seen in clinical trials of
cilomilast in the treatment of COPD. The side effects of diarrhea and nausea have been considerably higher with cilomilast versus
placebo, but these effects generally are tolerable and self limiting.
シロミラスト 上流と下流の製品情報
原材料
準備製品