Jan Peter Yska1, Ronald J Punter2, Herman J Woerdenbag3, Marloes Emous3, Henderik W Frijlink2, Bob Wilffert4,5, Eric N van Roon1,4. 1. Department of Clinical Pharmacy and Clinical Pharmacology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands. 2. Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands. 3. Department of Surgery, Medical Centre Leeuwarden, Leeuwarden, The Netherlands. 4. University of Groningen, Groningen Research Institute of Pharmacy, PharmacoTherapy, Epidemiology and Economics, Groningen, The Netherlands. 5. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract
BACKGROUND: The 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. OBJECTIVES: To 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. METHODS: With 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. RESULTS: From 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. CONCLUSIONS: This 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.
BACKGROUND: The 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. OBJECTIVES: To 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. METHODS: With 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. RESULTS: From 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. CONCLUSIONS: This 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.
Authors: R C A Schellekens; F E Stuurman; F H J van der Weert; J G W Kosterink; H W Frijlink Journal: Eur J Pharm Sci Date: 2006-10-04 Impact factor: 4.384
Authors: Jan Peter Yska; Jacquelien T M Wanders; Blessing Odigie; Jan A Apers; Marloes Emous; Erik R E Totté; E Christiaan Boerma; Froukje L Ubels; Herman J Woerdenbag; Henderik W Frijlink; Bob Wilffert; Eric N van Roon Journal: Eur J Hosp Pharm Date: 2019-02-15