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NISOLDIPINE: Clinical, biochemical, pharmacokinetic and experimental studies
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
1993 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nisoldipine is a new calcium channel blocker of the I ,4-dihydropyridine type. It possesses more vasoselective properties than nifedipine. Twenty-nine patients with different types of hypertension (normal renin hypertension, low renin hypertension and low renin hypertension combined with hypercalcaemia) and ten healthy subjects were investigated concerning the immediate effects of nisoldipine. The hypertensive patients received treatment for up to two years. Treattnent with nisoldipine caused an immediate reduction in blood pressure (BP) with the lowest BP values occurring after 6 hours and without reflexogenic tachycardia. The BP-lowering effect was sustained after 2 years' treatment. There were no significant differences regarding these effects between the different hypertensive patient groups. No adverse metabolic effects were observed. An immediate natriuretic and diuretic effect was established but no long-term effects could be found regarding the urinary excretion of sodium and water. Plasma renin activity rose slightly I hour after ingestion of nisoldipine, and the plasma aldosterone concentration decreased after 2 hours, but no clinically relevant long-term effects were seen regarding the renin-angiotensin-aldosterone-system. A slight rise in plasma noradrenaline concentration was noticed after the first dose of nisoldipine but there were no long-term effects on catecholarnines.

A new technique for the estimation of plasma concentrations of nisoldipine using a gas chromatograph - mass spectrometry method was developed. Plasma concentrations of nisoldipine rose rapidly after ingestion of 10 mg nisoldipine and peaked after a mean of I hour. A correlation was found between the plasma concentration of nisoldipine and the reduction in BP during steady-state conditions.

Nisoldipine has a marked relaxing effect on both bovine and human vein preparations in vitro and at a considerably lower concentration than the two reference substances nifedipine and glyceryl trinitrate. It was necessary to use a much higher concentration of nisoldipine to achieve relaxation of bovine mesenteric arteries than corresponding veins. 45ca++ influx was reduced in both bovine and human arteries after preexposure to nisoldipine.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1993. , 60 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 406
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-27535Local ID: 12192ISBN: 91-7870-944-XOAI: diva2:248087
Public defence
1993-12-10, Administrationsbyggnadens aula, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-07-23Bibliographically approved

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