The aim of this work was to correlate the in vitro human skin permeability, expressed as the permeability coefficient (Kp), and some physicochemical parameters of a new series of benzoxazinones. The in vitro human skin permeability of 14 substances, including regioisomers with CH3, OH, OCH3, and Cl groups in different positions on the aromatic ring, was determined. The modified Franz diffusion cell method was used. The Kp values were in the range 0.14-8.24 cm/h, showing a strong dependence on the position and type of substituent. Physicochemical descriptors usually referred in literature, such as log P, molecular weight and volume (MV), hydrogen bond donor (Hd) and acceptor activity (Ha), and molecular refractivity were considered, with the addition of solvation enthalpy (delta deltaHsolv). Delta deltaHsolv is defined as the difference between formation enthalpies in water and octanol. The algorithm with the best correlation between Kp and physicochemical descriptors was calculated, taking into account the differences observed among the regioisomers. The algorithm obtained with delta deltaHsolv had a good correlation (r2 = 0.749, F = 16.43, P = 0.0005), comparable with the equation, proposed by Potts and Guy, based on MV, Hd and Ha (r2 = 0.830, F = 16.3, P = 0.0004).

1999-02-01·European Journal of Pharmaceutical Sciences2区 · 医学

In vitro skin permeation of Sinitrodil, a member of a new class of nitrovasodilator drugs

2区 · 医学

Article

作者: P. Minghetti ; M.V. Monzani ; L. Montanari ; A. Casiraghi

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.

1997-09-01·Journal of Cardiovascular Pharmacology4区 · 医学

The Nitric Oxide Donor ITF 1129 Augments Subendocardial Blood Flow During Exercise-Induced Myocardial Ischemia

4区 · 医学

Article

作者: Robert J. Bache ; Dirk J. Duncker ; Jacques Mizrahi ; Yutaka Ishibashi

The effect of the nitric oxide donor ITF 1129 and nitroglycerin (NTG) on myocardial blood flow was examined in dogs with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD). Studies were performed during treadmill exercise in the presence of a coronary artery stenosis. The effects of ITF 1129 in doses of 3 and 10 micrograms/kg/min i.v. were compared with NTG (2 micrograms/kg/min i.v.). Neither ITF 1129 nor NTG caused significant alteration of heart rate, arterial blood pressure, or left ventricular systolic pressure. During partial inflation of the occluder to decrease distal coronary pressure to 55 +/- 2 mm Hg, mean myocardial blood flow measured with microspheres was 0.72 +/- 0.14 ml/min/g in the region perfused by the stenotic coronary artery compared with 2.93 +/- 0.40 ml/min/g in a normally perfused control region. With no change in distal coronary pressure, ITF 1129 increased mean myocardial blood flow in the stenosis perfused region to 1.15 +/- 0.24 ml/min/g (3 micrograms/kg/min i.v.) and to 1.20 +/- 0.28 ml/ min/g (10 micrograms/kg/min i.v.), whereas NTG (2 micrograms/kg/min iv) increased blood flow to 1.16 +/- 0.22 ml/min/g (each p < 0.05). The increase in myocardial blood flow produced by ITF 1129 or NTG occurred principally in the deeper myocardial layers with no change in subepicardial flow. As a result, the subendocardial/subepicardial blood flow ratio (ENDO/EPI) increased from 0.44 +/- 0.09 during control stenosis to 0.85 +/- 0.13 after ITF 1129 (10 micrograms/kg/min i.v.) and to 0.81 +/- 0.12 after NTG. Neither ITF 1129 nor NTG significantly altered myocardial blood flow in the normally perfused control region. The effect of ITF 1129 and NTG on myocardial perfusion occurred without alterations of distal coronary pressure or left ventricular diastolic pressure, indicating a primary effect on the intramural coronary microvasculature.

100 项与 ITF-1129 相关的药物交易

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