PMID: 2510657Jul 1, 1989Paper

Influence of acetylation phenotype on the pharmacokinetics and pharmacodynamics data of cadralazine in normotensive subjects

Archives des maladies du coeur et des vaisseaux
P BrunelJ Ménard

Abstract

Cadralazine is a new antihypertensive drug, acting as a peripheral arteriolar vasodilator through its hydrazinopyridazine metabolite. Since this metabolite actively contributes to the activity of the drug, we administered in a double blind randomized study 10 mg/placebo o.d. to 6 healthy fast and 6 slow normotensive acetylators in order to investigate the influence of the acetylator status on hemodynamics and pharmacokinetics. Blood pressure was measured with a DINAMAP apparatus, forearm hemodynamics with a pulsed doppler and central hemodynamics with impedance-cardiography; active renin (RIA), cadralazine and its metabolite (HPLC) were measured during the 11 measurement points. The results were analysed with repeated analysis of variance (ANOVA). Heart rate significantly increased (p less than 0.001), until the 24th hour (p less than 0.05), meanwhile blood pressure and forearm hemodynamics did not change. Cardiac output was increased as a consequence of the elevation in venous return. The rise in active renin paralleled the increase in heart rate with a significant correlation (r' = 0.580, p less than 0.05). The magnitude of the increase was higher in slow than that in fast acetylators, but did no reached the significance. No ...Continue Reading

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.