Циломиласт

Химические свойства

Cilomilast is White Solid

Использование

Cilomilast is a selective phosphodiesterase 4 (PDE4) inhibitor and can be used in treatment of chronic obstructive pulmonary disease.

Механизм действия

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.

Фармакокине?тика

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.