Current status of sustained release formulations in the treatment of hypertension. An overview.

The principal advantages to be gained from controlling the variables of drug release in sustained release formulations are as follows: (i) a more uniform plasma drug profile with fewer occasions when super- or subtherapeutic concentrations of the drug, or its active metabolite(s), occur; and (ii) a smoother therapeutic response over the dosage interval (provided the time-course of drug effects reflects the plasma concentration-time profile). Clinically, this offers the potential to optimise drug therapy and decrease the occurrence of concentration-related adverse effects. In addition, sustained release formulations may increase the likelihood of patient acceptance of therapy, and a once-daily sustained release formulation of a shorter-acting drug that provides a 'residual' therapeutic response at the end of the dosage interval can provide additional 'cover' in comparison with a once-daily conventional (immediate release) formulation. In the treatment of hypertension, there are potential advantages to be gained from continuous 24-hour control of blood pressure (BP), particularly in view of epidemiological evidence linking the apparent underperformance of antihypertensive therapy in some major intervention trials in reducing the occurrence of coronary heart disease to predicted levels with a relative failure to control diurnal BP fluctuations. In this regard, the concept of the trough:peak ratio as a measure of antihypertensive efficacy has gained increasing acceptance during recent years. A sustained release antihypertensive formulation offering an improved plasma concentration-time profile and an adequately high trough:peak ratio may therefore provide more consistent 24-hour BP-lowering activity, with attenuation of early morning BP surges and maximal target organ protection. This, coupled with the fact that sustained release formulations can also provide economic advantages in cardiovascular therapeutics by lowering overall health expenditure (which more than offsets their usually higher acquisition costs in comparison with immediate release formulations), suggests that they may have an increasingly important role to play in the future.