Donnelly R, Elliott H L, Meredith P A, Reid J L
University Department of Materia Medica, Stobhill General Hospital, Glasgow, UK.
J Hypertens Suppl. 1988 Dec;6(4):S643-5. doi: 10.1097/00004872-198812040-00202.
This study of ketanserin illustrates the use of concentration-effect analysis in clinical investigations of antihypertensive mechanisms and the factors responsible for interindividual differences in blood pressure response. Using an integrated kinetic-dynamic model the acute and chronic responses to ketanserin were characterized for each individual patient in terms of blood pressure fall per unit drug concentration. Two principal findings were obtained from this approach. (1) There was a significant reduction in responsiveness to ketanserin during chronic treatment: on average, -0.47 after the first dose compared with -0.25 mmHg/ng per ml after 1 month. (2) There was a significant change in the parameter keq, which characterizes the temporal discrepancy between the time profiles for plasma drug concentration and effect: from a mean value of 0.49 (first dose) to 1.86/h (1 month). There was no significant relationship between the responsiveness to ketanserin and patient age, peripheral alpha 1-adrenoceptor blockade or initial blood pressure. These results suggest that there is a change in the relative contributions of the component antihypertensive mechanisms during continued treatment with ketanserin. Furthermore, there is no clear relationship between patient age and responsiveness to ketanserin.
这项关于酮色林的研究阐述了浓度-效应分析在抗高血压机制临床研究中的应用，以及导致个体血压反应差异的因素。使用一个综合的动力学-动态模型，根据每位患者每单位药物浓度的血压下降情况，对酮色林的急性和慢性反应进行了表征。通过这种方法得出了两个主要发现。（1）慢性治疗期间对酮色林的反应性显著降低：首次给药后平均为-0.47，而1个月后为-0.25 mmHg/ng每毫升。（2）表征血浆药物浓度和效应时间曲线之间时间差异的参数keq发生了显著变化：从平均值0.49（首次给药）变为1.86/h（1个月）。对酮色林的反应性与患者年龄、外周α1-肾上腺素能受体阻断或初始血压之间没有显著关系。这些结果表明，在持续使用酮色林治疗期间，抗高血压机制各组成部分的相对贡献发生了变化。此外，患者年龄与对酮色林的反应性之间没有明确的关系。
