Conventional formulations of
metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of
hypertension and ischaemic
heart disease. Recently developed controlled release
metoprolol delivery systems (
metoprolol CR/ZOK and
metoprolol OROS) were designed to overcome the
drug delivery problems of matrix-based sustained release forms by releasing the
drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent
metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with
metoprolol CR/ZOK and
metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate
hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with
metoprolol CR/ZOK compared with matrix-based
sustained release formulations of
metoprolol, or conventional
atenolol or
bisoprolol, while
metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release
metoprolol preparations. In patients with stable effort
angina pectoris, once daily administration of
metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional
metoprolol in divided doses, while
metoprolol OROS reduced the mean number of anginal attacks by the same margin as
atenolol. Controlled release
metoprolol formulations have been well tolerated in clinical trials.
Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with
atenolol or long acting
propranolol.
Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated
bronchoconstrictor effects than
atenolol in asthmatics, and less general
fatigue and leg
fatigue in healthy subjects.
Metoprolol OROS produced less pronounced
bronchoconstrictor effects than
atenolol, matrix-based sustained release
metoprolol or long acting
propranolol in patients with
asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of
metoprolol in addition to the relatively low plasma concentrations maintained by
metoprolol CR/ZOK and
metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of
metoprolol, the use of all
beta-adrenoceptor antagonists should be avoided in patients with a history of
bronchospasm. Thus, controlled release
metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of
hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.