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Development and validation of simple, rapid and sensitive LC-PDA ultraviolet method for quantification of Nebivolol in rat plasma and its application to pharmacokinetic studies

100%

Ravi P. , Vats R. , Joseph S. , Gadekar N.

tom Vol. 27, no. 2

281--294

A simple, sensitive and rapid high-performance liquid chromatography method with ultraviolet (UV) detector was developed and validated for the analysis of Nebivolol (NBL) in rat plasma. The plasma sample, spiked with raloxifene hydrochloride as an internal standard (IS), was subjected to single step protein precipitation method prior to analysis. Chromatographic separation was achieved on the Agilent C8 (150 mm × 4.6 mm, 5 μm) column and monitored at a wavelength of 280 nm. Elution was carried out, in an isocratic mode, using a mobile phase consisting of acetonitrile and potassium di-hydrogen orthophosphate buffer (pH 3.5 ± 0.1) in the ratio of 37:63 v/v. Retention times of IS and NBL were 5.1 ± 0.10 min and 8.01 ± 0.12 min, respectively. No interference was observed from plasma components in the analysis of NBL and IS. Calibration curve was linear over the range of 125–3000 ng/mL (r2 = 0.999). NBL was found to be stable under various processing and storage conditions. The developed method was applied in the quantification of NBL in plasma samples, determining various pharmacokinetic parameters from intravenous bolus and oral administration of the drug in Wistar rats. NBL was found to follow two compartmental open models in Wistar rats.

NO-dependent vasodilation induced by nebivolol in coronary circulation is not mediated by beta-adrenoceptors or by 5 HT 1A-receptors

75%

Chlopicki S. , Kozlovski V. I. , Gryglewski R. J.

Journal of Physiology and Pharmacology

2002

tom 53

nr 4,1

Nebivolol is a unique ß1-adrenoceptor antagonist which possesses peripheral vasodilator properties dependent on endothelial NO. Nebivolol-induced release of NO was attributed to its L stereoisomer and to its ability to stimulate endothelial ß2, ß3 adrenoceptors or 5-HT1A receptors. Here, in the isolated guinea pig heart we analysed coronary vasodilator potency of L- and D-nebivolol and a possible role of ß2, ß3 adrenoceptors and 5-HT1A receptors in nebivolol-induced vasodilation. Surprisingly, we found that not only L-nebivolol (3-30x10-6 M) but also D-nebivolol (3-30x10-6 M) induced coronary vasodilation, and both responses were inhibited by L-NAME (10-4 M). In contrast with the stereoisomers of nebivolol, atenolol at the equimolar concentrations did induce slight vasoconstriction. The nonselective ß1/ß2- adrenoceptor antagonist - nadolol (10-5 M), the selective ß3-adrenoceptor antagonist - L 748337 (10-6 M) and the 5 HT1A receptor antagonist - NAN 190 (5 x 10-6 M), none of them inhibited coronary vasodilation induced by D- and L-nebivolol. In summary, in the isolated guinea pig heart both D- and L-nebivolol act as coronary vasodilators. Coronary vasodilation induced by stereoisomers of nebivolol is mediated by endothelium-derived NO and does not depend on ß2, ß3 adrenoceptors or 5 HT1A receptors.

Effect of nebivolol treatment on atherosclerotic plaque components in apoE-knockout mice

63%

Pyka-Fosciak G. , Jawien J. , Gajda M. , Jasek E. , Litwin J. A.

Journal of Physiology and Pharmacology

2013

tom 64

nr 6

The effect of nebivolol on atherogenesis in apoE - knockout mice

63%

Kus K. , Gajda M. , Pyka-Fosciak G. , Toton-Zuranska J. , Pawlowska M. , Suski M. , Niepsuj A. , Nowak B. , Wolkow P. , Olszanecki R. , Jawien J. , Korbut R.

Journal of Physiology and Pharmacology

2009

tom 60

nr 4

163-165

Nebivolol is a novel beta1-blocker with a nitric oxide (NO) - potentiating, vasodilatory effect that is unique among beta-blockers. It was already shown that nebivolol ameliorates atherosclerosis in cholesterol-fed rabbits. We, therefore, wanted to investigate whether this is the case in the fine experimental model of atherosclerosis: apolipoprotein E (apoE)- knockout mice. Nebivolol attenuated atherogenesis, measured both by "en face" method (9.23±1.8% vs. 14.6±2.1%) and "cross-section" method (63125±8455 µm2 vs. 91416±8357 m2). This is the first report showing the effect of nebivolol on atherogenesis in gene-targeted mice.

The influence of angiotensin-(1-7) peptidomimetic (AVE 0991) and nebivolol on angiotensin i metabolism in aorta of apoE-knockout mice

63%

Olszanecki R. , Suski M. , Gebska A. , Toton-Zuranska J. , Kus K. , Madej J. , Bujak-Gizycka B. , Jawien J. , Korbut R.

Journal of Physiology and Pharmacology

2013

tom 64

nr 3

Significant deterioration of anti-atherogenic efficacy of nebivolol in a double (apolipoprotein E and endothelial nitric oxide synthase) knockout mouse model of atherosclerosis in comparison to single (apolipoprotein E) knockout model

63%

Kus K. , Wisniewska A. , Toton-Zuranska J. , Olszanecki R. , Jawien J. , Korbut R.

nr 6