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

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 differences were found for AUC, Cmax and Tmax between the two groups but the active metabolite was eliminated slower than that of cadralazine. The time course of the effects on heart rate and plasma renin was not parallel to the plasma levels of cadralazine and its metabolite. With respect to the power of the study (1-beta = 80 p. 100), no significant differences were found between the two groups.