Дипивефрин

Adrenergic (ophthalmic).

Toovercome several of the pharmacokinetic and pharmaceuticalshortcomings of E as an ophthalmic agent, the prodrugapproach has been successfully applied. Dipivefrin is a prodrugof E that is formed by the esterification of the catecholOH groups of E with pivalic acid. Most of the advantages ofthis prodrug over E stem from improved bioavailability. Thegreatly increased lipophilicity allows much greater penetrabilityinto the eye through the corneal epithelial andendothelial layer. The stroma in between requires hydrophilicityfor penetration. Dipivefrin has that, too, due tothe 1-OH group and cationic nitrogen (the eyedrops containthe hydrochloride [HCl] salt). This dual solubility permitsmuch greater penetrability into the eye than the very hydrophilicE hydrochloride. Increased DOA is also achievedbecause the drug is resistant to the metabolism by COMT.In addition to its increased in vivo stability, it is also lesseasily oxidized by air due to the protection of the catecholOH groups. This high bioavailability and in vivo and in vitrostability translate into increased potency such that the 0.1%ophthalmic solution is approximately equivalent to a 2% Esolution. After its absorption, it is converted to E by esterasesslowly in the cornea and anterior chamber.Dipivefrin also offers the advantage of being less irritatingto the eye than E.