Donnelly R, Elliott H L, Meredith P A
Department of Medicine, Stanford University School of Medicine, Palo Alto, California.
Clin Pharmacokinet. 1994 Jun;26(6):472-85. doi: 10.2165/00003088-199426060-00005.
Although individualised antihypertensive therapy is widely recommended, prospective methods for optimising treatment are hampered by the paucity of basic information about dose-plasma concentration-response relationships for commonly used drugs. Concentration-effect analysis has been applied to a number of therapeutic areas. With antihypertensive drugs this approach has clearly identified direct relationships between pharmacokinetic and pharmacodynamic profiles within individual patients. Thus, either a linear or nonlinear model can be used to quantify the antihypertensive drug response in terms of parameters that incorporate pharmacokinetic and pharmacodynamic information. Furthermore, these models take account of placebo effects and time-dependent changes in blood pressure and drug concentrations during a dosage interval. Concentration-effect analysis has been used to characterise the responses to a range of calcium antagonist drugs. These studies have demonstrated that these analyses are useful for optimising dosage schedules, identifying determinants of blood pressure response, and predicting steady-state profiles of blood pressure (including peak/trough effects) after administration of a single ('test') dose. This mode of analysis warrants early inclusion in the clinical development of any new antihypertensive agent, so that the familiar difficulties in identifying the optimum dosage range are avoided.
尽管广泛推荐个体化抗高血压治疗，但由于缺乏常用药物剂量-血浆浓度-反应关系的基础信息，优化治疗的前瞻性方法受到阻碍。浓度-效应分析已应用于多个治疗领域。对于抗高血压药物，这种方法已明确确定个体患者体内药代动力学和药效学特征之间的直接关系。因此，线性或非线性模型均可用于根据纳入药代动力学和药效学信息的参数来量化抗高血压药物反应。此外，这些模型考虑了安慰剂效应以及给药间隔期间血压和药物浓度随时间的变化。浓度-效应分析已用于表征对一系列钙拮抗剂药物的反应。这些研究表明，这些分析对于优化给药方案、确定血压反应的决定因素以及预测单次（“试验”）给药后血压的稳态特征（包括峰/谷效应）很有用。这种分析模式值得在任何新型抗高血压药物的临床开发中尽早采用，以便避免在确定最佳剂量范围时常见的困难。
