Novel amides and esters prodrugs of olmesartan: Synthesis, bioconversion, and pharmacokinetic evaluation

Synthesis of novel amides and esters prodrugs of olmesartan is described. Their in vitro stability in rat plasma was tested. The results showed that the ester derivative IIa with n-octyl substituted dioxolone moiety was rapidly converted into olmesartan within 30 min. The pharmacokinetic parameters of IIa were studied and compared with those of olmesartan medoxomil. Compound IIa is proposed to be a promising prodrug of olmesartan.

Compound IIa was found to be well absorbed from rat gastrointestinal tract and rapidly converted into olmesartan. After oral administration of IIa, the Cmax and AUC values of olmesartan were significantly greater than those observed after oral administration of olmesartan medoxomil. Compound IIa is proposed to be an effective prodrug for olmesartan with improved oral bioavailability.Figure optionsDownload as PowerPoint slide