CONCENTRATION-EFFECT RELATIONSHIPS AND INDIVIDUAL-RESPONSES TO DOXAZOSIN IN ESSENTIAL-HYPERTENSION
CONCENTRATION-EFFECT RELATIONSHIPS AND INDIVIDUAL-RESPONSES TO DOXAZOSIN IN ESSENTIAL-HYPERTENSION
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DOI：
10.1111/j.1365-2125.1989.tb03537.x
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发表时间：
1989-11-01
影响因子：
3.4
通讯作者：
REID, JL
中科院分区：
文献类型：
--
作者：
DONNELLY, R;ELLIOTT, HL;REID, JL
本研究调查了10名原发性高血压患者在用α 1-肾上腺素受体拮抗剂多沙唑嗪急性和慢性治疗期间的药代动力学、药效学和浓度-效应关系方面。多沙唑嗪（2 mg）第一次给药后，血压显著降低，心率和血浆去甲肾上腺素增加，苯肾上腺素升压反应曲线平行移动，与α-肾上腺素受体拮抗作用对血管紧张素II的升压反应无显著变化。使用集成的动力学-动力学模型，个体血压反应性的特征为每单位药物浓度的血压下降（mmHg）。对多沙唑嗪首次给药的反应性与治疗1周和6周后的反应性直接相关，尽管在治疗第一周期间发生了系统性降低（约30%）。多沙唑嗪的急性或长期反应性均与年龄、血浆肾素活性、血浆去甲肾上腺素或苯肾上腺素治疗前敏感性无关。反应性与初始（治疗前）血压的高度之间存在显著相关性。药代动力学和药效学数据的整合提供了可重现的反应性指数，可用于研究长期抗高血压反应的一致性，确定影响反应程度的因素，并优化剂量和给药间隔的选择。
This study investigates aspects of the pharmacokinetics, pharmacodynamics and concentration-effect relationships in 10 patients with essential hypertension during acute and chronic treatment with doxazosin, an .alpha.1-adrenoceptor antagonist. Following the first dose of doxazosin (2 mg) there were significant reductions in blood pressures, increases in heart rate and in plasma noradrenaline, and parallel rightward shifts of the phenylephrine pressor response curves, consistent with .alpha.-adrenoceptor antagonism. There was no significant change in the pressor response to angiotensin II. Using an integrated kinetic-dynamic model, individual blood pressure responsiveness was characterised as the fall in blood pressure (mm Hg) per unit drug concentration. Responsiveness to the first dose of doxazosin was directly correlated with the responsiveness after 1 and 6 weeks treatment although there was a systematic reduction (of approximately 30%) which occurred during the first week of treatment. Neither the acute nor long-term responsiveness to doxazosin was related to age, plasma renin activity, plasma noradrenaline or the pretreatment sensitivity to phenylephrine. There was a significant relationship between responsiveness and the height of the initial (pretreatment) blood pressure. Integration of pharmacokinetic and pharmacodynamic data provides a reproducible index of responsiveness which can be used to investigate the consistency of the long-term anti-hypertensive response, to identify factors which influence the magnitude of the response, and to optimise the choice of dose and dose interval.