Influence of acetylator status on the haemodynamic effects and pharmacokinetics of cadralazine in healthy subjects. 1990

P Brunel, and J B Lecaillon, and T T Guyene, and P Imhof, and J Ménard
Pharmaceutical Research and Development Department, CIBA-GEIGY Limited, Basle, Switzerland.

1. Cadralazine is a new antihypertensive agent which causes peripheral vasodilation, probably mediated by a hydrazinopyridazine metabolite. 2. The possible influence of acetylator status on the pharmacokinetics and haemodynamics of the drug was studied in six fast and six slow acetylators over a period of 24 h after administration of a single 10 mg oral dose. 3. There were no differences between the two groups in AUC and Cmax values of cadralazine and apparent metabolite, the latter defined as the sum of the free and conjugated hydrazinopyridazine. Peak plasma concentrations of these compounds were reached after 1 h. Thereafter, the concentration of the metabolite declined more slowly than that of cadralazine. 4. No effects on blood pressure were noted. Changes in heart rate and plasma renin were delayed by 3-5 h with respect to the time-course of drug and metabolite in plasma; maximum responses occurred at 4-6 h after drug administration. The extent of the increase in plasma renin activity was slightly greater in slow than in fast acetylators, but the difference was not significant statistically.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011724 Pyridazines Six-membered rings with two adjacent nitrogen atoms also called 1,2-diazine.
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D012083 Renin A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19. Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D005542 Forearm Part of the upper extremity in humans and primates extending from the ELBOW to the WRIST. Antebrachium,Antebrachiums,Forearms
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic

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