Bisoprolol PM
Bisoprolol PM is a novel formulation of the beta-adrenergic blocking agent (beta blocker), bisoprolol. It is marketed at present in the US and Europe as an immediate release product, for the management of hypertension and in Europe also for the treatment of angina and CHD. The regulatory approval strategy for this product will be a 505(b)(2) NDA which may help shorten the development and approval times for this product.At present, the maximal effect of bisoprolol occurs within 1-4 hours post dosing and persists for 24 hours. Since bisoprolol is administered once-daily in the morning, the maximum effect does not occur at the time of highest risk of cardiac events (i.e. upon waking). In order to optimise the effect during waking hours and to minimise side effects, a product that can be administered in the evening with onset beginning prior to waking the next morning would provide full coverage during waking hours. In addition, such a mode of drug exposure should have a significant impact on the incidence of major cardiovascular events in the early morning period.
The Bisoprolol PM formulation has been designed to be administered in the evening just before bed with onset of action occurring prior to the patient waking in the morning, not hours after waking. This allows the patient to be treated optimally during all waking hours of the day and in particular provides maximum exposure in the early morning high-risk period. Bisoprolol PM is designed to minimise drug-release for 4 hours after dosing at night to coincide with the early sleeping period, which is the lowest daily risk period for cardiovascular events. Thereafter, the drug is released from the formulation in a manner whereby therapeutic concentrations are achieved prior to wakening, the highest risk period for cardiovascular events, and maintained throughout the remainder of the dosing interval.