BackgroundThe Roux-en-Y gastric bypass (RYGB) is a bariatric procedure, greatly reducing the stomach size and bypassing the duodenum and proximal jejunum. Hence, RYGB may reduce the absorption and bioavailability of oral medication. For clinical decisions on the use of medication, knowledge of altered modifications in drug disposition is a prerequisite. An in vitro dissolution method for solid oral medications, simulating conditions before and after RYGB, might be a valuable tool to predict the pharmaceutical availability of medicines frequently used by patients after RYGB.ObjectivesTo develop a gastrointestinal simulation system (GISS), mimicking conditions before and after RYGB for investigating dissolution characteristics of solid oral medications, and to assess the pharmaceutical availability of metoprolol from immediate-release (IR) and controlled-release (CR) tablets under these conditions.MethodsWith an adjusted, pharmacopoeial paddle dissolution apparatus, the GISS enables variation in parameters which are relevant to drug release in vivo: pH, volume, residence time, osmolality and agitation. Metoprolol tartrate 100 mg IR tablets and metoprolol CR tablets were tested. Release profiles were determined by measuring the concentrations of metoprolol spectrophotometrically.ResultsFrom IR tablets, under all conditions applied, >85% of metoprolol was released within 25 min. From all tested CR tablets >90% of metoprolol was released after 22 hours.ConclusionsThis GISS is a suitable dissolution system to assess pharmaceutical availability before and after RYGB. In patients who have undergone RYGB, no problems in pharmaceutical availability of metoprolol IR and CR tablets are to be expected. Any changes in response to metoprolol in patients after RYGB should therefore be ascribed to changes in bioavailability.

Introduction Dopamine D2 (DA2) agonists are a first line treatment option in young Parkinson's patients with mild to moderate symptoms. DA2 agonists are known to cause depression of cardiac functions with decrease in heart rate. A recent European multicentre study [1] found a relationship between the use of DA2 agonists in Parkinson's disease (PD) and heart failure (HF) especially in early phase of therapy.