Sustained release, rationale

Knopp RH. Clinical profiles of plain versus sustained-release niacin (Niaspan) and the physiologic rationale for nighttime dosing. Am J Cardiol 1998 82(12A) 24U-28U ... 

L-Dopa is a prodrug of dopamine and is known as the drug of choice for the treatment of Parkinson s disease. L-Dopa has a narrow absorption window and is actively absorbed from the upper part of the small intestine. The large fluctuations in L-Dopa plasma concentration cause severe side effects. Hence, there is a PK rationale to elevate the extent of absorption while minimizing the maximum plasma concentration (Cmax) obtained, following oral administration of a sustained release (SR) formulation of L-Dopa. 

Sustained release (SR) preparations are not new but several new modifications are being introduced. They are also referred to as long acting or delayed release when compared to rapid or conventional release preparations. The term sometimes overlaps with controlled release, which implies more sophisticated control of release and not just confined to the time dimension. Controlled release implies consistency, but release of drug in SR preparations may not be consistent. The following are the rationale of developing SR ... 

The rationale behind controlled or sustained release has always been the need for a therapeutic drug level that is sufficient without the overdose level that is generally found with injection or other forms of bolus medicant delivery. Oftentimes, there are undesirable side effects associated with bolus drug delivery and, in the case of certain drug therapies, a second drug must be administered to prevent side effects such as nausea. In theory, a properly designed controlled delivery device should overcome or minimize problems associated with pulsed drug delivery. 

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