A gastrointestinal simulation system for dissolution of oral solid dosage forms before and after Roux-en-Y gastric bypass.
Roux-en-Y gastric bypass
controlled release
dissolution
gastrointestinal simulation system
metoprolol
pharmaceutical availability
Journal
European journal of hospital pharmacy : science and practice
ISSN: 2047-9956
Titre abrégé: Eur J Hosp Pharm
Pays: England
ID NLM: 101578294
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
23
07
2017
revised:
13
01
2018
accepted:
22
01
2018
entrez:
21
8
2019
pubmed:
21
8
2019
medline:
21
8
2019
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
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
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
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
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.
Identifiants
pubmed: 31428323
doi: 10.1136/ejhpharm-2017-001360
pii: ejhpharm-2017-001360
pmc: PMC6684018
doi:
Types de publication
Journal Article
Langues
eng
Pagination
152-156Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
Psychosomatics. 2005 May-Jun;46(3):250-3
pubmed: 15883146
Pharm Res. 2006 Jan;23(1):165-76
pubmed: 16308672
Am J Health Syst Pharm. 2006 Oct 1;63(19):1852-7
pubmed: 16990631
Eur J Pharm Sci. 2007 Jan;30(1):15-20
pubmed: 17085024
Clin Pharmacokinet. 1991 Nov;21(5):319-30
pubmed: 1773547
Obes Rev. 2010 Jan;11(1):41-50
pubmed: 19493300
Mol Pharm. 2010 Oct 4;7(5):1388-405
pubmed: 20822152
Am J Health Syst Pharm. 2011 Dec 1;68(23):2241-7
pubmed: 22095812
Obes Surg. 2012 Aug;22(8):1263-7
pubmed: 22527599
Surg Obes Relat Dis. 2013 Sep-Oct;9(5):714-7
pubmed: 22571886
Expert Opin Drug Metab Toxicol. 2012 Dec;8(12):1505-19
pubmed: 22998066
J Clin Pharmacol. 2013 Apr;53(4):361-76
pubmed: 23381905
Obes Surg. 2013 Jun;23(6):819-25
pubmed: 23430479
Cochrane Database Syst Rev. 2014 Aug 08;(8):CD003641
pubmed: 25105982
Eur J Clin Pharmacol. 2016 Feb;72(2):203-9
pubmed: 26525890
Obes Surg. 2017 Apr;27(4):1076-1090
pubmed: 28124236
Obes Surg. 2017 Sep;27(9):2279-2289
pubmed: 28405878
Gastroenterology. 1986 Apr;90(4):958-62
pubmed: 3949122
Pharm Res. 1998 Jun;15(6):889-96
pubmed: 9647355