Concentration-effect analysis of antihypertensive drug response. Focus on calcium antagonists

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.