In vitro skin permeation of Sinitrodil, a member of a new class of nitrovasodilator drugs.
Clinical trials have shown the potential of benzoxazinones, a new class of organic nitrates, in cardiovascular therapy. In particular Sinitrodil possesses a coronary vascular selectivity greater than that of Nitroglycerin and isosorbide dinitrate. The objective of this study was a preliminary evaluation of the ability of these new organic nitrate derivatives to reach therapeutical steady-state plasma concentrations following a transdermal administration. In vitro permeation studies through human stratum corneum and epidermis have been conducted on two members of this class: Sinitrodil (ITF 296) and ITF 1129. Comparative studies have also been carried out with Nitroglycerin, Isosorbide dinitrate and Nicorandil. Two different fixed concentrations were tested: 0.08% w/v solution and saturated solution. Sinitrodil could be considered a good candidate for transdermal administration on the basis of the in vitro permeation results and of the known therapeutical plasma concentration.
Minghetti
P
P
Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Milano, viale Abruzzi 42, 20131 Milano, Italia. paola.minghetti@unimi.it
Casiraghi
A
A
Montanari
L
L
Monzani
M V
MV
D048588:Benzoxazines; D006801:Humans; D066298:In Vitro Techniques; D009566:Nitrates / Q000097:blood / Q000493:pharmacokinetics*; D010078:Oxazines / Q000097:blood / Q000493:pharmacokinetics*; D012869:Skin Absorption; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics*
D048588:Benzoxazines; D009566:Nitrates; D010078:Oxazines; D014665:Vasodilator Agents; C091726:sinitrodil