Reid J L, Meredith P A
Department of Medicine and Therapeutics, University of Glasgow, Scotland.
Hypertension. 1990 Jul;16(1):12-8. doi: 10.1161/01.hyp.16.1.12.
It is now widely recognized that a rigid stepped-care approach to antihypertensive therapy is not universally appropriate. Individualized treatment may result in good or better blood pressure control and a simpler regimen without troublesome side effects. Successful development of such a strategy depends on accurate characterization of a dose-response relation and quantitative assessment of the response in each individual. In the past such relations have proved to be hard to identify for antihypertensive drugs, often because of inappropriate study design during drug development. Despite failure of earlier studies to identify drug concentration-antihypertensive response relations, use of concentration-effect modeling, which recognizes and characterizes the temporal discrepancy between drug concentration and effect, has proved more successful. By using such approach, it has been possible to characterize the concentration-effect relations after acute and steady-state antihypertensive therapy with prazosin, doxazosin, nifedipine, verapamil, and enalapril. With enalapril and nifedipine, it has been demonstrated that the mathematical parameters of effect derived from the first dose can predict the response to these drugs after 4-6 weeks of treatment. These findings suggest that the definition of individual concentration-effect relations may be of value in the rational choice of antihypertensive drug therapy and optimization of dose and dose frequency. In particular, the approach can provide valuable information on dose-effect relations and should optimize choice of dose intervals in drug development and practice.
现在人们普遍认识到，采用严格的阶梯式降压治疗方法并非普遍适用。个体化治疗可能会使血压得到良好或更好的控制，治疗方案更简单，且无麻烦的副作用。制定这样一种策略的成功取决于准确描述剂量反应关系以及对每个个体反应的定量评估。过去，由于药物研发过程中研究设计不当，抗高血压药物的此类关系往往难以确定。尽管早期研究未能确定药物浓度与抗高血压反应的关系，但使用能够识别和描述药物浓度与效应之间时间差异的浓度效应模型已被证明更为成功。通过使用这种方法，已经能够描述哌唑嗪、多沙唑嗪、硝苯地平、维拉帕米和依那普利急性和稳态抗高血压治疗后的浓度效应关系。对于依那普利和硝苯地平，已经证明从首剂得出的效应数学参数可以预测治疗4至6周后对这些药物的反应。这些发现表明，个体浓度效应关系的定义可能有助于合理选择抗高血压药物治疗以及优化剂量和给药频率。特别是，该方法可以提供有关剂量效应关系的有价值信息，并应在药物研发和实践中优化给药间隔的选择。
