Choosing the optimal antihypertensive dose regimen.

THE OPTIMAL DOSE-RESPONSE CURVE: From a pharmacological point of view the optimal dose regimen of an antihypertensive agent is relatively easy to define. By constructing dose-response curves the most effective dose can usually be identified. From a clinical point of view the problem is more complicated. FACTORS THAT INFLUENCE THE IDEAL CLINICAL DOSE: The most important consideration is the relationship between efficacy and adverse effects. Ideally, dose-response curves for both antihypertensive efficacy and adverse effects should be produced. From these curves the optimal dose may be established. Drugs such as lacidipine that demonstrate a good overlap between efficacy and tolerability provide a wide therapeutic window. PRACTICAL CONSIDERATIONS: It may be less effective to increase the dose of a single drug until the desired effect is obtained; the addition of another therapeutic agent is often preferable. Cost is also a factor. If the dose-response curve flattens, it may not be cost-effective to recommend a higher dose, even if the higher dose is slightly more effective. Furthermore, if an unnecessarily high dose has been recommended, doctors will soon learn to prescribe half the dose or less, which may have budgetary implications for the manufacturer. The choice of the optimal dose regimen is a complicated, multifactorial problem. The aim is to find a reasonable balance between efficacy and adverse effects, at a competitive cost.